Drug-sensitive FGFR3 mutations in lung ...

Annals of Oncology Advance Access published December 19, 2016

Original article Drug-sensitive FGFR3 mutations in lung adenocarcinoma P. Chandrani1,2*, K. Prabhash2,3*, A. Choughule3, R. Prasad1, V. Sethunath1, M. Ranjan1, P. Iyer1,2, J. Aich1, H. Dhamne1, D. N. Iyer1, P. Upadhyay1,2, B. Mohanty4, P. Chandna5, R. Kumar3, A. Joshi3, V. Noronha3, V. Patil3, A. Ramaswamy3, A. Karpe3, R. Thorat4, P. Chaudhari4, A. Ingle4, A. Dutt1,2 1 Integrated Genomics Laboratory, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India

Mumbai, India 3 Department of Medical Oncology, Tata Memorial Hospital, Tata Memorial Centre, Mumbai, India 4 Small Animal Imaging Facility, Animal Sciences, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, India 5 AceProbe Technologies Pvt. Ltd., New Delhi, India * Both authors contributed equally

Correspondence should be addressed to:

Dr. Amit Dutt Wellcome Trust/ DBT India Alliance Intermediate Fellow Tata Memorial Centre, ACTREC Navi Mumbai, 410 210 INDIA. Phone: +91-22-27405056 Email address: [email protected] © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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2 Homi Bhabha National Institute, Training School Complex, Anushakti Nagar,

Abstract

Background: Lung cancer is the leading cause of cancer-related deaths across the world. In this study we present therapeutically relevant genetic alterations in lung adenocarcinoma of Indian origin. Materials and methods: Forty-five primary lung adenocarcinoma tumors were sequenced for 676 amplicons using RainDance cancer panel at an average coverage of 1500X (reads per million mapped reads). To validate the findings, 49 mutations across 23 genes were genotyped in an additional set of 363 primary lung adenocarcinoma tumors using mass spectrometry. NIH/3T3 cells over expressing

independent growth, constitutive activation, tumor formation and sensitivity to FGFR inhibitors using in vitro and xenograft mouse models Results: We present the first spectrum of actionable alterations in lung adenocarcinoma tumors of Indian origin, and show that mutations of FGFR3 are present in 20 of 363 (5.5%) patients. These FGFR3 mutations are constitutively active and oncogenic when ectopically expressed in NIH/3T3 cells and using a xenograft model in NOD/SCID mice. Inhibition of FGFR3 kinase activity inhibits transformation of NIH/3T3 overexpressing FGFR3 constructs and growth of tumors driven by FGFR3 in the xenograft models. The reduction in tumor size in the mouse is paralleled by a reduction in the amounts of phospho-ERK, validating the in vitro findings. Interestingly, the FGFR3 mutations are significantly higher in a proportion of younger patients and show a trend towards better overall survival, compared to patients lacking actionable alterations or those harboring KRAS mutations. Conclusion: We present the first actionable mutation spectrum in Indian lung cancer genome. These findings implicate FGFR3 as a novel therapeutic in lung adenocarcinoma.

Keywords: lung adenocarcinoma; actionable mutations; fibroblast growth factor receptor 3; oncogene; FGFR inhibitors; mass spectrometry

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mutant and wild type FGFR3 constructs were characterized for anchorage

Key Message

Diversity in cancer-specific alterations lends similarity to the known plurality in clinical response based on ethnicity and other divergent factors. This study establishes that FGFR3 mutations found in lung adenocarcinoma patients of Indian origin are oncogenic, and forms a subclass of FGFR inhibitor-sensitive patients largely distinct from those harboring EGFR, KRAS, or EML4-ALK mutations.


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Introduction

Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for over a million deaths annually [1]. Molecularly targeted therapies improve outcome for lung adenocarcinoma patients whose tumors harbor mutant EGFR or translocated ALK, RET, or ROS1, with an encouraging response for those with mutated BRAF, MET, NTRK-1 & 2 and ERBB2 [2-5]. Such oncogenic somatic alterations though vary across populations/ethnic groups, e.g., EGFR mutations are present in over 30% of East Asian lung adenocarcinoma patients, however, they are only found in about 23-25% of Indian and 10% of Western lung adenocarcinoma

Indian lung adenocarcinoma patients than compared to the Caucasian population [3, 9, 10]. The diversity in somatic alterations lends similarity to the known plurality in clinical response based on ethnicity and divergent genetic and environmental factors [11], Thus, besides the unmet need for additional therapeutic targets in lung adenocarcinoma patients, it is equally pertinent to profile known oncogenic somatic alterations across different populations to understand their landscape of variability. Here, in an attempt to profile for activating alterations, we have generated a comprehensive mutational spectrum of activating alterations prevalent among lung adenocarcinoma patients of Indian origin, considered to be an admixture population of non-European Caucasian and Ancestral South Indians. We also report the first incidence of activating and drug sensitive FGFR3 mutations in lung adenocarcinoma. FGFR3 mutated samples, with ~5% population frequency, form a distinct subclass apart from EGFR, KRAS, and EML4-ALK.

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patients [6-8]. Similarly, KRAS mutations are present at 60% lower frequency in

Methods & Materials

Patients To profile for therapeutically relevant genome alterations in lung adenocarcinoma of Indian origin, FFPE blocks with known EGFR mutation status for 45 consecutive histologically confirmed lung adenocarcinoma patients tumor samples (stage IV, 49% males and 51% non-smokers) for sequencing and an additional set of 363 consecutive lung adenocarcinoma patients tumor samples (stage IV, 62% males and 73% non-smokers) for mass spectrometry were retrospectively collected from Tata

Pooling of samples, target gene-capturing and next generation sequencing A set of 45 lung adenocarcinoma samples were sequenced using pooled sequencing approach to capture low frequency variants [12-14]. Briefly, 45 samples were divided into duplicate pools of different population size (Supplementary Figure-S1) i.e. 2 pools of 5 individuals (5XA and 5XB), 2 pools of 10 individuals (10XA and 10XB), and, 1 pool of 15 individuals (15X) for next-generation sequencing (NGS) of 676 genomic regions of 158 genes as described earlier [15]. Discovery of genomic variants using computational analysis FASTQ files were analyzed using BWA-Picard-GATK/MuTect pipeline generating 3349 unique variants (Supplementary Table S2). Polymorphisms overlapping with dbSNP database (v.142) and Indian specific SNP database TMC-SNPdb derived from whole exome sequencing of 62 normal samples [16] were filtered (Supplementary Figure S2, S3). Stringent mutation analysis was performed as further detailed in supplementary methods to derive list of significant mutations for further validation (Supplementary Table S2 and S3). Mass spectrometry based genotyping Briefly, PCR and extension primers for 49 mutations in 23 genes were designed using single base extension based mass spectrometry assay design 3.1 software

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Memorial Hospital (Supplementary Table S1).

(Supplementary Table S4). Mutation calls were analysed using Typer 4 (Sequenom Inc., USA) and were reviewed by manually observing mass-spectra. Cell culture, anchorage-independent growth assay and immunoblotting NIH/3T3 cells transduced with FGFR3 wild-type and mutant construct were used for induction and drug inhibition study as detailed in supplementary methods. Anchorage independent growth assay and immunoblotting were performed as described earlier [17], and as detailed in the supplementary methods. Xenograft development

5 million cells for tumor formation in 2-3 months. Inhibitor BGJ-398 [18] was given at 15 and 30 mg/kg along with vehicle control (10% tween-80) independently to randomised xenograft groups after tumor size reaching ~150 mm3. Tumor size was measured every alternate day using Vernier calliper for 14 days’ drug treatment. microPET-CT scan was performed at the end of the drug treatment. Immunohistochemistry Immunohistochemistry analysis was performed as described earlier [19] and detailed in supplementary methods. Overall survival analysis Overall survival of patients was assessed using Kaplan-Meier method using R and IBM SPSS software package, as detailed in supplementary methods. The end point was taken as date of death with censoring implied at the date of the last contact.

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A cohort of 8 NOD-SCID or Nude mice per clone were subcutaneously injected with

Results

Recurrent FGFR3 mutations in lung adenocarcinoma patient of Indian origin To identify low frequency and ethnic specific therapeutically relevant genome alterations in lung adenocarcinoma of Indian origin, we sequenced 45 primary lung adenocarcinoma stage IV tumors (Supplementary Table S1) for 676 amplicons at an average coverage of 1500X (reads per million mapped reads), as described in Supplementary Figure S1-S5; Supplementary Table S2 & S3. To validate the findings, we selected 49 mutations occurring across 23 genes based on their recurrence and therapeutic significance (Supplementary Table S4), for genotyping in

Supplementary Table S5) using mass spectrometry. Based on the mutation profiling of 363 lung adenocarcinoma patients, we present the first portrait of activating mutations present in the Indian lung cancer genome (Figure 1B), wherein 160 of 363 patients were found to harbor activating mutations across 8 genes at following frequency: EGFR (28.4%), KRAS (13%), ALK (3.8%), AKT1 (2.5%), PIK3CA (1.4%), FGFR4 (0.4%), and ERBB2 (0.3%) as shown in Figure 1A, consistent with earlier reports [6, 8, 9]. In addition, 3 of 79 patients were found to harbor EML4-ALK translocation as determined by FISH. Among the other most significantly mutated genes, we found recurrent FGFR3 mutations in 20 of 363 tumors (5.5%), of which 7 co-occurred in samples harboring EGFR (n=5) and KRAS (n=2) mutation. In total, sixteen patients harbored FGFR3 (S249C) mutation; and, 4 patients harbored a novel FGFR3 (G691R) mutation (Figure 1A; Figure 1C upper panel; Supplementary Figure S6; Supplementary Table S6). Interestingly, FGFR3 (S249C) mutation has previously been described as activating and drug sensitive in lung squamous [20], while the novel FGFR3 (G691R) mutation was predicted to be deleterious based on using 7 of 10 functional prediction tools (Supplementary Table S3). FGFR3 mutations in lung adenocarcinoma are activating in-vitro & in-vivo To test whether the recurrent FGFR3 mutations found in this study are activating we transduced NIH/3T3 fibroblast cells with retroviruses encoding the FGFR3 G691R

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an additional set of 363 primary lung adenocarcinoma stage IV tumors (Figure 1A;

mutation along with WT FGFR3 and the previously characterized FGFR3 (R248C) and (S249C) mutations [20]. Similar to FGFR3 R248C and S249C, the ectopic expression of the novel G691R mutant clone in pooled NIH/3T3 cells conferred anchorage-independent growth, forming 3-fold more colonies in soft agar than cells expressing WT FGFR3 (Figure 1C left panel), despite higher expression levels of WT FGFR3 (Figure 1C right panel). The transformation was accompanied by elevated phosphorylation of the downstream ERK1/2 and AKT1 in a constitutive manner (Figure 1D). Further, consistent with the in vitro data, NIH/3T3 cells expressing transforming FGFR3 mutations or WT when injected subcutaneously into NOD/SCID mice formed tumors within 2 months post injection of cells. While 3 of 11

injected with cells expressing FGFR3 S249C; and, 6 of 12 mice injected with cells expressing FGFR3 G691R formed tumors (Figure 1E). The tumor size doubling time was ~7 days for cells expressing FGFR3 (G691R), ~5 days for cells expressing FGFR3 (S249C); the FGFR3-WT tumors doubled in size in ~9-10 days. FGFR3 mutations in lung adenocarcinoma are sensitive to inhibitors in-vitro & in-vivo We further show that inhibition of FGFR3 kinase activity using pan FGFR inhibitor PD173074 block the constitutive phosphorylation of ERK1/2 (Figure 2A). Similarly, treatment of cells harboring activating FGFR3 mutations with PD173074 result in a marked decrease in colony formation in soft agar and cell survival in liquid culture (Figure 2B). Extending the effect in vivo studies, when tumors reached approximately 100-200 mm3 in all mice injected with NIH/3T3 cells began treatment with 15 or 30 mg/kg BGJ398 – a selective FGFR inhibitor currently under clinical trials for various cancer types (as PD173074 is incompatible with in vivo studies [21]), or vehicle for 14 days. Tumors treated with BGJ398 slowed or reversed their growth compared with vehicle (Figure 2C upper panel), so that by the end of the study, the effect on tumor burden in vehicle-treated versus BGJ398-treated mice were 3.3 folds in FGFR3 (S249C), 3 folds in FGFR3 (G691R) and 2.25 folds in FGFR3-WT xenografts (Figure 2D). This reduction in tumor size was paralleled by a reduction in the amounts of phospho-ERK1/2 in immuno-histochemical analyses

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mice injected with cells expressing FGFR3 WT formed tumors, 12 of 12 mice

(Figure 2C lower panel) of explanted tumors, validating our in vitro findings that MAPK signaling is the key pathway engaged by mutated FGFR3. Correlation of FGFR3 mutations with clinicopathological features of lung cancer patients Clinically, lung adenocarcinoma patients with FGFR3 mutation positive tumors expressing higher activated MAPK levels (Supplementary Figure S7) show a better trend in overall survival (OS) with 17 months (n= 8; 95% CI: 6.4-27.5; HR: 0.6) compared to 14 months (n= 197; 95% CI: 8.7-13.2) in patients with wild-type FGFR3 (Figure 2E). The OS trend in lung adenocarcinoma patients though is similar to

head & neck cancer and lung squamous carcinoma patients, based on our analysis using cBioPortal for survival of patients harboring activating FGFR3 mutations in different cancers (Supplementary Figure S8). Furthermore, the FGFR3 mutations were observed to be significantly higher in patients < 45 years (9 of 95) than in patients > 45 years (11 of 269) (P = 0.048) but not with their gender and smoking status (Supplementary Table S7). The sample size in this study, however, is underpowered to reach statistical significance for survival data.

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bladder urothelial carcinomas and skin cutaneous melanoma patients, but not to

Discussion

We

present

the

first

portrait

of

clinically

actionable

alterations

in

lung

adenocarcinoma of Indian origin which includes EGFR, KRAS, EML4-ALK, AKT1, PIK3CA, FGFR4 and ERBB2, similar to that identified in other ethnic groups [5, 22, 23], and an additional subset of patients with FGFR3 mutations. Ethnic-specific variations have been well known in lung cancer [24, 25] across different populations. We observed 28.4% EGFR mutations and 13% KRAS mutations in lung adenocarcinoma patients, consistent with our previous report [6, 9]. Similarly, variation in frequency of other molecular alterations is also observed such as 3%

5% Chinese population [23]. ERBB2 mutation found at A c.(748-750)GGG>AGG p.G250R ABL1_uc004bzv.2_Missense_Mu g.chr5:112170822C>T uc010jby.2 0 15 2298 c.1918C>T c.(1918-1920)CGG>TGG p.R640W APC_uc011cvt.1_Missense_Muta g.chr5:112175396C>T uc010jby.2 0 16 4485 c.4105C>T c.(4105-4107)CCC>TCC p.P1369S APC_uc011cvt.1_Missense_Muta g.chr5:112175550C>T uc010jby.2 0 16 4639 c.4259C>T c.(4258-4260)CCC>CTC p.P1420L APC_uc011cvt.1_Missense_Muta g.chr5:112175735C>T uc010jby.2 0 16 4824 c.4444C>T c.(4444-4446)CTT>TTT p.L1482F APC_uc011cvt.1_Missense_Muta g.chr5:112176038A>G uc010jby.2 0 16 5127 c.4747A>G c.(4747-4749)ATG>GTG p.M1583V APC_uc011cvt.1_Missense_Muta g.chr7:140481397C>T uc003vwc.3 0 11 1472 c.1411G>A c.(1411-1413)GTC>ATC p.V471I g.chr7:140481418C>T uc003vwc.3 0 11 1451 c.1390G>A c.(1390-1392)GGA>AGA p.G464R g.chr16:68842417C>T uc002ewg.1 0 4 602 c.478C>T c.(478-480)CCC>TCC p.P160S CDH1_uc010vlj.1_RNA|CDH1_uc g.chr16:68847276G>A uc002ewg.1 0 9 1322 c.1198G>A c.(1198-1200)GAT>AAT p.D400N CDH1_uc010vlj.1_RNA|CDH1_uc g.chr16:68857418G>A uc002ewg.1 0 13 2177 c.2053G>A c.(2053-2055)GTG>ATG p.V685M CDH1_uc010vlj.1_RNA|CDH1_uc g.chr9:21974723C>T uc003zpk.2 MTAP_uc003zpi.1_Intron|CDKN2 0 1 316 c.104G>A c.(103-105)GGG>GAG p.G35E g.chr5:149441342G>A uc003lrl.2 0 11 1892 c.1697C>T c.(1696-1698)CCC>CTC p.P566L CSF1R_uc011dcd.1_Missense_M g.chr7:55242464_55242479AGGAATTAAGAGAAGC>A c.(2233-2250)AAGGAATTAAGAGAAGCA>AAA p.ELREA746del EGFR_uc010kzg.1_In_Frame_De uc003tqk.2 0 19 2480_2495 c.2234_2249AGGAATTAAGAGAAGC>A g.chr7:55249005G>T EGFR_uc010kzg.1_Missense_Mu uc003tqk.2 0 20 2549 c.2303G>T c.(2302-2304)AGC>ATC p.S768I g.chr7:55249023T>C uc003tqk.2 0 20 2567 c.2321T>C c.(2320-2322)GTG>GCG p.V774A EGFR_uc010kzg.1_Missense_Mu g.chr7:55249037G>A uc003tqk.2 0 20 2581 c.2335G>A c.(2335-2337)GGC>AGC p.G779S EGFR_uc010kzg.1_Missense_Mu g.chr7:55259433C>T uc003tqk.2 0 21 2737 c.2491C>T c.(2491-2493)CGT>TGT p.R831C EGFR_uc010kzg.1_Missense_Mu g.chr7:55259443T>C uc003tqk.2 0 21 2747 c.2501T>C c.(2500-2502)GTG>GCG p.V834A EGFR_uc010kzg.1_Missense_Mu g.chr7:55259514C>A uc003tqk.2 0 21 2818 c.2572C>A c.(2572-2574)CTG>ATG p.L858M EGFR_uc010kzg.1_Missense_Mu g.chr7:55259515T>G uc003tqk.2 0 21 2819 c.2573T>G c.(2572-2574)CTG>CGG p.L858R EGFR_uc010kzg.1_Missense_Mu g.chr4:1803413T>C uc003gdr.3 0 6 938 c.682T>C c.(682-684)TGC>CGC p.C228R FGFR3_uc003gdu.2_Missense_M g.chr4:1803568C>G uc003gdr.3 0 7 1002 c.746C>G c.(745-747)TCC>TGC p.S249C FGFR3_uc003gdu.2_Missense_M g.chr4:1803669C>T uc003gdr.3 0 7 1103 c.847C>T c.(847-849)CCC>TCC p.P283S FGFR3_uc003gdu.2_Missense_M g.chr4:1808278C>T uc003gdr.3 0 16 2292 c.2036C>T c.(2035-2037)TCC>TTC p.S679F FGFR3_uc003gdu.2_Missense_M g.chr4:1808313G>A uc003gdr.3 0 16 2327 c.2071G>A c.(2071-2073)GGG>AGG p.G691R FGFR3_uc003gdu.2_Missense_M g.chr13:28608116C>T uc001urw.2 0 15 1932 c.1850G>A c.(1849-1851)GGA>GAA p.G617E FLT3_uc010aao.2_RNA|FLT3_uc g.chr7:99526685C>T uc011kjd.1 0 1 559 c.559G>A c.(559-561)GAG>AAG p.E187K g.chr9:5072541G>A uc010mhm.2 0 12 1804 c.1691G>A c.(1690-1692)CGA>CAA p.R564Q JAK2_uc003ziw.2_Missense_Mut g.chr9:5072622C>T uc010mhm.2 0 12 1885 c.1772C>T c.(1771-1773)TCA>TTA p.S591L JAK2_uc003ziw.2_Missense_Mut g.chr4:55593586C>T uc010igr.2 0 11 1739 c.1652C>T c.(1651-1653)CCC>CTC p.P551L KIT_uc010igs.2_Missense_Mutat g.chr4:55593627G>A uc010igr.2 0 11 1780 c.1693G>A c.(1693-1695)GGA>AGA p.G565R KIT_uc010igs.2_Missense_Mutat g.chr4:55598153G>A uc010igr.2 0 16 2437 c.2350G>A c.(2350-2352)GCC>ACC p.A784T KIT_uc010igs.2_Missense_Mutat g.chr12:25380283C>T uc001rgp.1 KRAS_uc001rgq.1_Missense_Mu 0 3 356 c.175G>A c.(175-177)GCA>ACA p.A59T g.chr12:25398218G>A uc001rgp.1 KRAS_uc001rgq.1_Missense_Mu 0 2 282 c.101C>T c.(100-102)CCA>CTA p.P34L g.chr12:25398284C>A uc001rgp.1 KRAS_uc001rgq.1_Missense_Mu 0 2 216 c.35G>T c.(34-36)GGT>GTT p.G12V g.chr19:814532C>T uc002lpx.1 0 7 797 c.733G>A c.(733-735)GCG>ACG p.A245T LPPR3_uc010dru.1_Missense_M g.chr7:116422067G>A uc003vij.2 0 18 3735 c.3548G>A c.(3547-3549)GGC>GAC p.G1183D MET_uc010lkh.2_Missense_Muta g.chr3:37050365G>A uc003cgl.2 0 6 574 c.514G>A c.(514-516)GAA>AAA p.E172K MLH1_uc011aye.1_5'UTR|MLH1_ g.chr3:37058999C>T uc003cgl.2 0 10 853 c.793C>T c.(793-795)CGT>TGT p.R265C MLH1_uc011aye.1_Missense_Mu g.chr3:37090083C>T MLH1_uc011aye.1_Missense_Mu uc003cgl.2 0 17 2032 c.1972C>T c.(1972-1974)CTT>TTT p.L658F g.chr3:37090446G>A uc003cgl.2 0 18 2101 c.2041G>A c.(2041-2043)GCT>ACT p.A681T MLH1_uc011aye.1_Missense_Mu g.chr2:47703527C>T uc002rvy.1 0 13 2095 c.2027C>T c.(2026-2028)TCA>TTA p.S676L MSH2_uc010yoh.1_Missense_Mu g.chr2:47705428C>T uc002rvy.1 0 14 2296 c.2228C>T c.(2227-2229)TCA>TTA p.S743L MSH2_uc010yoh.1_Missense_Mu

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

14 15 4 6 11 11 12 34 34 26 4 12 12 3 6 6 6 6 6 6 6 8 8 9 23 12 12 15 15 16 4 2 1 10 8 8 8 8 8 8 8 7 7 6 6 6 5

2340 2532 841 1030 1465 1557 1695 7532 7528 4781 795 2039 2097 1120 1345 1398 1407 1410 1417 1420 1428 1711 1783 2046 2558 2352 2457 2807 2862 2924 2246 1982 1834 1233 1032 1024 1021 1012 1005 1000 979 883 882 852 816 766 718

c.2272G>A c.(2272-2274)GAT>AAT p.D758N MSH2_uc010yoh.1_Missense_Mu c.2464T>C c.(2464-2466)TGT>CGT p.C822R MSH2_uc010yoh.1_Missense_Mu c.398G>A c.(397-399)TGC>TAC p.C133Y NF2_uc003afy.3_Missense_Muta c.587G>A c.(586-588)CGA>CAA p.R196Q NF2_uc003afy.3_Missense_Muta c.1022G>A c.(1021-1023)CGA>CAA p.R341Q NF2_uc003afy.3_Missense_Muta c.1114G>A c.(1114-1116)GAA>AAA p.E372K NF2_uc003afy.3_Missense_Muta c.1252C>T c.(1252-1254)CGC>TGC p.R418C NF2_uc003afy.3_Missense_Muta c.7532C>T c.(7531-7533)ACC>ATC p.T2511I c.7528C>T c.(7528-7530)CTC>TTC p.L2510F c.4781G>A c.(4780-4782)CGG>CAG p.R1594Q NOTCH1_uc004cia.1_Missense_ c.464C>T c.(463-465)CCC>CTC p.P155L PDGFRA_uc003haa.2_Intron|PDG c.1708C>T c.(1708-1710)CAT>TAT p.H570Y PDGFRA_uc003haa.2_Intron|PDG c.1766C>A c.(1765-1767)CCA>CAA p.P589Q PDGFRA_uc003haa.2_Missense c.89C>T c.(88-90)CCA>CTA p.P30L c.314G>A c.(313-315)TGT>TAT p.C105Y c.367C>T c.(367-369)CAC>TAC p.H123Y c.376G>A c.(376-378)GCT>ACT p.A126T c.379G>A c.(379-381)GGA>AGA p.G127R c.386G>A c.(385-387)GGA>GAA p.G129E c.389G>A c.(388-390)CGA>CAA p.R130Q c.397G>A c.(397-399)GTA>ATA p.V133I c.680C>T c.(679-681)TCC>TTC p.S227F c.752G>A c.(751-753)GGT>GAT p.G251D c.1015C>T c.(1015-1017)CCA>TCA p.P339S c.2392C>T c.(2392-2394)CGG>TGG p.R798W c.2162G>A c.(2161-2163)CGG>CAG p.R721Q RET_uc001jak.1_Missense_Muta c.2267C>T c.(2266-2268)GCC>GTC p.A756V RET_uc001jak.1_Missense_Muta c.2617C>T c.(2617-2619)CGG>TGG p.R873W RET_uc001jak.1_Missense_Muta c.2672C>T c.(2671-2673)TCG>TTG p.S891L RET_uc001jak.1_Missense_Muta c.2734C>T c.(2734-2736)CGG>TGG p.R912W RET_uc001jak.1_Missense_Muta c.668G>A c.(667-669)CGT>CAT p.R223H RUNX1_uc002yui.2_Intron|RUNX c.404G>A c.(403-405)AGG>AAG p.R135K RUNX1_uc002yui.2_Missense_M RUNX1_uc002yut.1_RNA|RUNX1 c.256C>T c.(256-258)CCC>TCC p.P86S c.1039G>A c.(1039-1041)GCC>ACC p.A347T TP53_uc002gig.1_Intron|TP53_uc c.838A>G c.(838-840)AGA>GGA p.R280G TP53_uc002gig.1_Intron|TP53_uc c.830G>T c.(829-831)TGT>TTT p.C277F TP53_uc002gig.1_Intron|TP53_uc c.827C>T c.(826-828)GCC>GTC p.A276V TP53_uc002gig.1_Intron|TP53_uc c.818G>A c.(817-819)CGT>CAT p.R273H TP53_uc002gig.1_Intron|TP53_uc c.811G>A c.(811-813)GAG>AAG p.E271K TP53_uc002gig.1_Intron|TP53_uc TP53_uc002gig.1_Intron|TP53_uc c.806G>T c.(805-807)AGC>ATC p.S269I c.785G>T c.(784-786)GGT>GTT p.G262V TP53_uc002gig.1_Intron|TP53_uc TP53_uc002gig.1_Missense_Mut c.689C>T c.(688-690)ACC>ATC p.T230I c.688A>G c.(688-690)ACC>GCC p.T230A TP53_uc002gig.1_Missense_Mut c.658T>A c.(658-660)TAT>AAT p.Y220N TP53_uc002gig.1_Missense_Mut c.622G>A c.(622-624)GAC>AAC p.D208N TP53_uc002gig.1_Missense_Mut c.572C>A c.(571-573)CCT>CAT p.P191H TP53_uc002gig.1_Missense_Mut c.524G>A c.(523-525)CGC>CAC p.R175H TP53_uc002gig.1_Missense_Mut Downloaded from http://annonc.oxfordjournals.org/ by guest on December 26, 2016

g.chr2:47705472G>A uc002rvy.1 g.chr2:47707840T>C uc002rvy.1 g.chr22:30038225G>A uc003age.3 g.chr22:30051653G>A uc003age.3 g.chr22:30067837G>A uc003age.3 g.chr22:30067929G>A uc003age.3 g.chr22:30069387C>T uc003age.3 g.chr9:139390659G>A uc004chz.2 g.chr9:139390663G>A uc004chz.2 g.chr9:139399362C>T uc004chz.2 g.chr4:55129930C>T uc003han.3 g.chr4:55141062C>T uc003han.3 g.chr4:55141120C>A uc003han.3 g.chr10:89653791C>T uc001kfb.2 g.chr10:89692830G>A uc001kfb.2 g.chr10:89692883C>T uc001kfb.2 g.chr10:89692892G>A uc001kfb.2 g.chr10:89692895G>A uc001kfb.2 g.chr10:89692902G>A uc001kfb.2 g.chr10:89692905G>A uc001kfb.2 g.chr10:89692913G>A uc001kfb.2 g.chr10:89717655C>T uc001kfb.2 g.chr10:89717727G>A uc001kfb.2 g.chr10:89720864C>T uc001kfb.2 g.chr13:49039407C>T uc001vcb.2 g.chr10:43612057G>A uc001jal.2 g.chr10:43612162C>T uc001jal.2 g.chr10:43615538C>T uc001jal.2 g.chr10:43615593C>T uc001jal.2 g.chr10:43617397C>T uc001jal.2 g.chr21:36206763C>T uc002yuh.2 g.chr21:36252877C>T uc002yuh.2 g.chr21:36259154G>A uc002yuh.2 g.chr17:7573988C>T uc002gim.2 g.chr17:7577100T>C uc002gim.2 g.chr17:7577108C>A uc002gim.2 g.chr17:7577111G>A uc002gim.2 g.chr17:7577120C>T uc002gim.2 g.chr17:7577127C>T uc002gim.2 g.chr17:7577132C>A uc002gim.2 g.chr17:7577153C>A uc002gim.2 g.chr17:7577592G>A uc002gim.2 g.chr17:7577593T>C uc002gim.2 g.chr17:7578191A>T uc002gim.2 g.chr17:7578227C>T uc002gim.2 g.chr17:7578277G>T uc002gim.2 g.chr17:7578406C>T uc002gim.2

g.chr17:7578418T>C uc002gim.2 g.chr17:7578508C>T uc002gim.2 g.chr17:7578518C>T uc002gim.2 g.chr17:7578542G>A uc002gim.2 g.chr17:7579313G>A uc002gim.2 g.chr17:7579334G>A uc002gim.2 g.chr3:10183752T>C uc003bvc.2 g.chr3:10188288G>A uc003bvc.2

0 0 0 0 0 0 0 0

5 5 5 5 4 4 1 2

706 616 606 582 568 547 434 644

c.512A>G c.422G>A c.412G>A c.388C>T c.374C>T c.353C>T c.221T>C c.431G>A

c.(511-513)GAG>GGG p.E171G TP53_uc002gig.1_Missense_Mut c.(421-423)TGC>TAC p.C141Y TP53_uc002gig.1_Missense_Mut c.(412-414)GCC>ACC p.A138T TP53_uc002gig.1_Missense_Mut c.(388-390)CTC>TTC TP53_uc002gig.1_Missense_Mut p.L130F c.(373-375)ACG>ATG p.T125M TP53_uc002gig.1_Missense_Mut c.(352-354)ACA>ATA TP53_uc002gig.1_Missense_Mut p.T118I c.(220-222)GTC>GCC VHL_uc003bvd.2_Missense_Muta p.V74A c.(430-432)GGA>GAA p.G144E VHL_uc003bvd.2_Intron



Refseq_mRNA_Id Refseq_prot_Id SwissProt_acc_Id SwissProt_entry_Id DescriptionUniProt_AApos UniProt_Region UniProt_Natural_Variations UniProt_Experimental_Info NM_005157NP_005148P00519 ABL1_HUMAN c-abl oncogene 1, receptor tyrosine kinase 250 Protein kinase.|ATP. NM_001127511 NP_001120983 APC_HUMAN adenomatous polyposis coli P25054 640 Leu-rich.|ARM 5. NM_001127511 NP_001120983 APC_HUMAN adenomatous polyposis coli P25054 1369 Ser-rich. NM_001127511 NP_001120983 APC_HUMAN adenomatous polyposis coli P25054 1420 Ser-rich. NM_001127511 NP_001120983 APC_HUMAN adenomatous polyposis coli P25054 1482 Ser-rich. NM_001127511 NP_001120983 APC_HUMAN adenomatous polyposis coli P25054 1583 Ser-rich. NM_004333NP_004324P15056 BRAF_HUMAN B-Raf 471 ATP (By similarity).|Protein kinase. NM_004333NP_004324P15056 BRAF_HUMAN G -> E (in colorectal kinase. cancer).|G -> V (in a colo B-Raf 464 ATP (By similarity).|Protein NM_004360NP_004351P12830 CADH1_HUMAN cadherin 1, type 1 preproprotein 160 Cadherin 1.|Extracellular (Potential). NM_004360NP_004351P12830 CADH1_HUMAN cadherin 1, type 1 preproprotein Missing (in a gastric (Potential). carcinoma sample; loss o 400 Cadherin 3.|Extracellular NM_004360NP_004351P12830 CADH1_HUMAN cadherin 1, type 1 preproprotein 685 Cadherin 5.|Extracellular (Potential). NM_000077NP_000068P42771 CD2A1_HUMAN cyclin-dependent kinase inhibitor -> V (in1CMM2; loss of CDK4 binding).|G -> 35 ANK 1. 2AGisoform NM_005211NP_005202P07333 CSF1R_HUMAN colony stimulating factor 1 receptor precursor 566 Cytoplasmic (Potential). NM_005228NP_005219P00533 EGFR_HUMAN epidermal growth factorCytoplasmic receptor isoform Missing (Potential).|Protein a (found in a lung kinase. cancer sample). 746_750 NM_005228NP_005219P00533 EGFR_HUMAN epidermal growth factor receptor isoform (Potential).|Protein a kinase. 768 Cytoplasmic NM_005228NP_005219P00533 EGFR_HUMAN epidermal growth factor receptor isoform (Potential).|Protein a kinase. 774 Cytoplasmic NM_005228NP_005219P00533 EGFR_HUMAN epidermal growth factor receptor isoform (Potential).|Protein a kinase. 779 Cytoplasmic NM_005228NP_005219P00533 EGFR_HUMAN epidermal growth factor receptor isoform (Potential).|Protein a kinase. 831 Cytoplasmic NM_005228NP_005219P00533 EGFR_HUMAN epidermal growth factor receptor isoform V(Potential).|Protein -> La(found in a lung kinase. cancer sample). 834 Cytoplasmic NM_005228NP_005219P00533 EGFR_HUMAN epidermal growth factor receptor isoform L(Potential).|Protein -> Ra(found in a lung kinase. cancer sample; somat 858 Cytoplasmic NM_005228NP_005219P00533 EGFR_HUMAN epidermal growth factor receptor isoform L(Potential).|Protein -> Ra(found in a lung kinase. cancer sample; somat 858 Cytoplasmic NM_000142NP_000133P22607 FGFR3_HUMAN fibroblast growth factor receptor 3 isoform C(Potential).|Ig-like -> R 1 (in a colorectal C2-type adenocarcinoma 2. samp 228 Extracellular NM_000142NP_000133P22607 FGFR3_HUMAN fibroblast growth factor receptor 3 isoform S(Potential). -> C (in 1 KERSEB, bladder cancer, cervical 249 Extracellular NM_000142NP_000133P22607 FGFR3_HUMAN fibroblast growth factor receptor C2-type 3 isoform 3.|Extracellular 1 (Potential). 283 Ig-like NM_000142NP_000133P22607 FGFR3_HUMAN fibroblast growth factor receptorkinase.|Cytoplasmic 3 isoform 1 (Potential). 679 Protein NM_000142NP_000133P22607 FGFR3_HUMAN fibroblast growth factor receptorkinase.|Cytoplasmic 3 isoform 1 (Potential). 691 Protein NM_004119NP_004110P36888 FLT3_HUMAN fms-related tyrosine617 kinase Protein 3 precursor kinase.|ATP (By similarity).|Cytoplasmic (Potentia NM_181538NP_853516Q8NFK1 CXG3_HUMAN gap junction protein, gamma 3, 30.2kDa 187 Extracellular (Potential). NM_004972NP_004963O60674 JAK2_HUMAN Janus kinase 2 564 Protein kinase 1. NM_004972NP_004963O60674 JAK2_HUMAN Janus kinase 2 591 Protein kinase 1. NM_000222NP_000213P10721 KIT_HUMAN v-kit Hardy-Zuckerman 4 feline sarcoma Missing (Potential). viral (in GIST; somatic mutation).|Missing 551 Cytoplasmic NM_000222NP_000213P10721 KIT_HUMAN v-kit Hardy-Zuckerman 4 feline sarcoma viral 565 Cytoplasmic (Potential). NM_000222NP_000213P10721 KIT_HUMAN v-kit Hardy-Zuckerman 4 feline kinase.|Cytoplasmic sarcoma viral (Potential). 784 Protein NM_033360NP_203524P01116 RASK_HUMAN c-K-ras2 protein isoform a precursorA -> T (in bladder cancer and GASC; somatic 59 GTP. NM_033360NP_203524P01116 RASK_HUMAN c-K-ras2 protein isoform a precursor region. P -> R (in CFC syndrome; characterized by a 34 Effector NM_033360NP_203524P01116 RASK_HUMAN c-K-ras2 protein isoform a precursorG -> D (in pancreatic carcinoma, GASC and l 12 GTP. NM_024888NP_079164Q6T4P5 LPPR3_HUMAN plasticity-related protein 2 245 Helical; (Potential). NM_000245NP_000236P08581 MET_HUMAN met proto-oncogene isoform Protein b precursor kinase.|Cytoplasmic (Potential). 1183 NM_000249NP_000240P40692 MLH1_HUMAN MutL protein homolog 1721 NM_000249NP_000240P40692 MLH1_HUMAN MutL protein homolog R -> C (associated with HNPCC2; results in p 2651 NM_000249NP_000240P40692 MLH1_HUMAN MutL protein homolog 6581 NM_000249NP_000240P40692 MLH1_HUMAN MutL protein homolog A -> T (in HNPCC2; could be a common poly 6811 NM_000251NP_000242P43246 MSH2_HUMAN mutS homolog 2 676 ATP (Potential). NM_000251NP_000242P43246 MSH2_HUMAN mutS homolog 2 743

MSH2_HUMAN mutS homolog 2 758 MSH2_HUMAN mutS homolog 2 822 MERL_HUMAN neurofibromin 2 isoform 1 133 FERM. C -> R (in NF2). MERL_HUMAN neurofibromin 2 isoform 1 196 FERM. MERL_HUMAN neurofibromin 2 isoform 1 341 Glu-rich. MERL_HUMAN neurofibromin 2 isoform 1 372 Glu-rich. MERL_HUMAN neurofibromin 2 isoform 1 R -> C (in vestibular schwannoma). 418 Glu-rich. NOTC1_HUMAN notch1 preproprotein 2511 Cytoplasmic (Potential). NOTC1_HUMAN notch1 preproprotein 2510 Cytoplasmic (Potential). NOTC1_HUMAN notch1 preproprotein 1594 Extracellular (Potential). PGFRA_HUMAN platelet-derived growth factor receptor (Potential).|Ig-like alpha C2-type 2. 155 Extracellular PGFRA_HUMAN platelet-derived growth factor receptor alpha 570 Cytoplasmic (Potential). PGFRA_HUMAN platelet-derived growth factor receptor alpha 589 Cytoplasmic (Potential). PTEN_HUMAN phosphatase and tensin homolog 30 Phosphatase tensin-type. PTEN_HUMAN phosphatase and tensin homolog C tensin-type. -> F (in BZS; loss of phosphatase activity to 105 Phosphatase PTEN_HUMAN phosphatase and tensin homolog H tensin-type. -> R (in CD).|H -> Y (in endometrial cancer 123 Phosphatase PTEN_HUMAN phosphatase and tensin homolog 126 Phosphatase tensin-type. PTEN_HUMAN phosphatase and tensin homolog 127 Phosphatase tensin-type. PTEN_HUMAN phosphatase and tensin homolog G tensin-type. -> E (in CD; no lipid phosphatase activity b 129 Phosphatase PTEN_HUMAN phosphatase and tensin homolog R tensin-type. -> L (in CD R->M: and endometrial Does not affect hyperplasia; the abilitylot 130 Phosphatase PTEN_HUMAN phosphatase and tensin homolog V tensin-type. -> I (loss of phosphatase activity towards In 133 Phosphatase PTEN_HUMAN phosphatase and tensin homolog tensin-type. S -> F (reduced phosphatase activity towards 227 C2 PTEN_HUMAN phosphatase and tensin homolog tensin-type. G -> C (loss of phosphatase activity towards I 251 C2 PTEN_HUMAN phosphatase and tensin homolog 339 C2 tensin-type. RB_HUMANretinoblastoma 1 798 Interaction with LIMD1.|Domain C; mediates interaction w RET_HUMAN ret proto-oncogene721 isoform a Cytoplasmic (Potential). RET_HUMAN ret proto-oncogene756 isoform Protein a kinase.|Cytoplasmic (Potential). RET_HUMAN ret proto-oncogene873 isoform Protein a kinase.|Cytoplasmic R -> Q (in HSCR1; (Potential). sporadic form). RET_HUMAN ret proto-oncogene891 isoform Protein a kinase.|Cytoplasmic S -> A (in MTC; familial (Potential). form). RET_HUMAN ret proto-oncogene912 isoform Protein a kinase.|Cytoplasmic (Potential). RUNX1_HUMAN runt-related transcription factor 1 isoform Missing: No DNA-binding. 223 Pro/Ser/Thr-rich. RUNX1_HUMAN runt-related transcription factor 1 isoform with DNA.|Runt. R->A: Strongly reduces DNA-bind 135 Interaction RUNX1_HUMAN runt-related transcription factor 1 isoform 86 Runt. P53_HUMAN tumor protein p53 isoform a A -> T (in sporadic with cancers; HIPK1 (By somatic similarity).|Int mutation 347 Oligomerization.|Interaction P53_HUMAN tumor protein p53 isoform a with R ->DNA.||Interaction T (in sporadic cancers; with E4F1.|Interaction somatic mutation w 280 Interaction P53_HUMAN tumor protein p53 isoform a with C ->DNA.||Interaction W (in sporadic cancers; with E4F1.|Interaction somatic mutatiow 277 Interaction P53_HUMAN tumor protein p53 isoform a with A ->DNA.||Interaction V (in sporadic cancers; with E4F1.|Interaction somatic mutation w 276 Interaction P53_HUMAN tumor protein p53 isoform a with R ->DNA.||Interaction N (in a sporadic cancer; with E4F1.|Interaction somatic mutatiow 273 Interaction P53_HUMAN tumor protein p53 isoform a E with -> E4F1.|Interaction D (in sporadic cancers; with HIPK1 somatic (Bymutation similari 271 |Interaction P53_HUMAN tumor protein p53 isoform a S with -> E4F1.|Interaction I (in a sporadic cancer; with HIPK1 somatic (Bymutation similari 269 |Interaction P53_HUMAN tumor protein p53 isoform a GN with-> E4F1.|Interaction PD (in a sporadic with cancer; HIPK1somatic (By similari muta 262 |Interaction P53_HUMAN tumor protein p53 isoform a forTinteraction -> S (in sporadic with FBXO42.||Interaction cancers; somatic mutation with HI 230 Required P53_HUMAN tumor protein p53 isoform a forTinteraction -> S (in sporadic with FBXO42.||Interaction cancers; somatic mutation with HI 230 Required P53_HUMAN tumor protein p53 isoform a forYinteraction -> N (in sporadic with FBXO42.||Interaction cancers; somatic mutation with HI 220 Required P53_HUMAN tumor protein p53 isoform a forDinteraction -> E (in sporadic with FBXO42.||Interaction cancers; somatic mutation with HI 208 Required P53_HUMAN tumor protein p53 isoform a forPinteraction -> R (in sporadic with FBXO42.||Interaction cancers; somatic mutation with HI 191 Required P53_HUMAN tumor protein p53 isoform a forRinteraction -> L (in LFS; withgermline FBXO42.||Interaction mutation and in with spor HI 175 Required Downloaded from http://annonc.oxfordjournals.org/ by guest on December 26, 2016

NM_000251NP_000242P43246 NM_000251NP_000242P43246 NM_000268NP_000259P35240 NM_000268NP_000259P35240 NM_000268NP_000259P35240 NM_000268NP_000259P35240 NM_000268NP_000259P35240 NM_017617NP_060087P46531 NM_017617NP_060087P46531 NM_017617NP_060087P46531 NM_006206NP_006197P16234 NM_006206NP_006197P16234 NM_006206NP_006197P16234 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000314NP_000305P60484 NM_000321NP_000312P06400 NM_020975NP_066124P07949 NM_020975NP_066124P07949 NM_020975NP_066124P07949 NM_020975NP_066124P07949 NM_020975NP_066124P07949 NM_001001890 NP_001001890 Q01196 NM_001001890 NP_001001890 Q01196 NM_001001890 NP_001001890 Q01196 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637

NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_001126112 NP_001119584 P04637 NM_000551NP_000542P40337 NM_000551NP_000542P40337

P53_HUMAN tumor protein p53 isoform a forEinteraction -> G (in sporadic with FBXO42.||Interaction cancers; somatic mutation with HI 171 Required P53_HUMAN tumor protein p53 isoform a forCinteraction -> A (in a sporadic with FBXO42.||Interaction cancer; somatic mutatio with HI 141 Required P53_HUMAN tumor protein p53 isoform a forAinteraction -> D (in sporadic with FBXO42.||Interaction cancers; somatic mutation with HI 138 Required P53_HUMAN tumor protein p53 isoform a forL interaction -> H (in sporadic with FBXO42.||Interaction cancers; somatic mutation with HI 130 Required P53_HUMAN tumor protein p53 isoform a forTinteraction -> A (in a sporadic with FBXO42.||Interaction cancer; somatic mutation with HI 125 Required P53_HUMAN tumor protein p53 isoform a forTinteraction -> I (in sporadic with FBXO42.||Interaction cancers; somatic mutation) with HI 118 Required VHL_HUMAN von Hippel-Lindau tumor 74 suppressor isoform 1 VHL_HUMAN von Hippel-Lindau 144 tumor Involved suppressor in binding isoform to 1CCT complex.



GO_Biological_Process GO_Cellular_Component GO_Molecular_Function Polyphen2_HVAR_pred MutationAssessor_pred SIFT_pred Polyphen2_HDIV_pred LRT_pred MutationTaster_pred actin cytoskeleton cytoskeleton|cytosol|nuclear organization|axon ATP binding|DNA membrane|nucleolus|perinuclear binding|magnesium adhesion|DNA damage ion binding|mitogen-activated induced protein phosphorylation|D protein kina D guidance|blood D;D coagulation|cell D;Dion binding|manganese D region ofDcytoplasm N canonical Wnt adherens receptor junction|APC-Axin-1-beta-catenin beta-catenin signaling pathway|cell adhesion|cell complex|Axin-APC-beta-catenin-GSK3B cycle binding|microtubule arrest|cell migration|cellular plus-end binding|protein component complex|beta-catenin kinase disassembly binding|protein destructi involved Dbinding|gamma-catenin D;D D;D D D M canonical Wnt adherens receptor junction|APC-Axin-1-beta-catenin beta-catenin signaling pathway|cell adhesion|cell complex|Axin-APC-beta-catenin-GSK3B cycle binding|microtubule arrest|cell migration|cellular plus-end binding|protein component complex|beta-catenin kinase disassembly binding|protein destructi involved . binding|gamma-catenin D;D D;D D D L canonical Wnt adherens receptor junction|APC-Axin-1-beta-catenin beta-catenin signaling pathway|cell adhesion|cell complex|Axin-APC-beta-catenin-GSK3B cycle binding|microtubule arrest|cell migration|cellular plus-end binding|protein component complex|beta-catenin kinase disassembly binding|protein destructi involved . binding|gamma-catenin D;D P;P D D M canonical Wnt adherens receptor junction|APC-Axin-1-beta-catenin beta-catenin signaling pathway|cell adhesion|cell complex|Axin-APC-beta-catenin-GSK3B cycle binding|microtubule arrest|cell migration|cellular plus-end binding|protein component complex|beta-catenin kinase disassembly binding|protein destructi involved . binding|gamma-catenin D;D D;D D D L canonical Wnt adherens receptor junction|APC-Axin-1-beta-catenin beta-catenin signaling pathway|cell adhesion|cell complex|Axin-APC-beta-catenin-GSK3B cycle binding|microtubule arrest|cell migration|cellular plus-end binding|protein component complex|beta-catenin kinase disassembly binding|protein destructi involved . binding|gamma-catenin D;D D;D D D L activation ofcytosol|nucleus|plasma MAPKK activity|anti-apoptosis|nerve ATP binding|metal membrane ion binding D B growth factor B receptor D signaling pathway|organ D M morphogenesis|positive regula activation ofcytosol|nucleus|plasma MAPKK activity|anti-apoptosis|nerve ATP binding|metal membrane ion binding D D growth factor D receptor D signaling pathway|organ D H morphogenesis|positive regula adherens junction actin cytoskeleton|aggresome|apical organization|cellular cell adhesion component binding|gamma-catenin junction disassembly complex|catenin incomplex|cell-cell apoptosis|cellular adherens response junction|endosome|focal to indole-3-methanol|cel a D molecule D;D D;D involved Dbinding D M adherens junction actin cytoskeleton|aggresome|apical organization|cellular cell adhesion component binding|gamma-catenin junction disassembly complex|catenin involved incomplex|cell-cell apoptosis|cellular adherens response junction|endosome|focal to indole-3-methanol|cel a D molecule D D Dbinding D H adherens junction actin cytoskeleton|aggresome|apical organization|cellular cell adhesion component binding|gamma-catenin junction disassembly complex|catenin incomplex|cell-cell apoptosis|cellular adherens response junction|endosome|focal to indole-3-methanol|cel a D molecule D;D D;P involved Dbinding D M cell cycle arrest|cell cytosol|nucleus cycle cyclin-dependent checkpoint|G1 phase protein ofkinase mitoticinhibitor cell activity|NF-kappaB mitotic cell binding|protein of apoptosis|ne binding|prote D D;D D;Dcycle|G1/S . transitionDofbinding|protein H cycle|induction cell proliferation|multicellular integral to plasma ATP binding|cytokine organismal membrane|receptor development|transmembrane binding|macrophage colony-stimulating receptor protein tyrosine receptor activity|protein signaling pathway homodimeriz D D;DcomplexD;D D D factor Mkinase activation ofbasolateral phospholipase plasma actinA2 filament activity membrane|endoplasmic binding|ATP by calcium-mediated binding|double-stranded reticulum signaling|activation membrane|endosome|extracellular DNAof binding|epidermal phospholipase Cgrowth activity|axon space|Golgi factor receptor guidance|cell membrane|int activitp activation ofbasolateral phospholipase plasma actinA2 filament activity membrane|endoplasmic by calcium-mediated reticulum signaling|activation membrane|endosome|extracellular binding|epidermal phospholipase activity|axon space|Golgi factor receptor guidance|cell membrane|int activitp D binding|ATP D;Dbinding|double-stranded P;D D DNAof D M Cgrowth activation ofbasolateral phospholipase plasma actinA2 filament activity membrane|endoplasmic by calcium-mediated reticulum signaling|activation membrane|endosome|extracellular binding|epidermal phospholipase activity|axon space|Golgi factor receptor guidance|cell membrane|int activitp D binding|ATP P;Dbinding|double-stranded P;D D DNAof D M Cgrowth activation ofbasolateral phospholipase plasma actinA2 filament activity membrane|endoplasmic by calcium-mediated reticulum signaling|activation membrane|endosome|extracellular binding|epidermal phospholipase activity|axon space|Golgi factor receptor guidance|cell membrane|int activitp D binding|ATP D;Dbinding|double-stranded D;D D DNAof D H Cgrowth activation ofbasolateral phospholipase plasma actinA2 filament activity membrane|endoplasmic by calcium-mediated reticulum signaling|activation membrane|endosome|extracellular binding|epidermal phospholipase activity|axon space|Golgi factor receptor guidance|cell membrane|int activitp D binding|ATP D;Dbinding|double-stranded B;D D DNAof D L Cgrowth activation ofbasolateral phospholipase plasma actinA2 filament activity membrane|endoplasmic by calcium-mediated reticulum signaling|activation membrane|endosome|extracellular binding|epidermal phospholipase activity|axon space|Golgi factor receptor guidance|cell membrane|int activitp D binding|ATP D;Dbinding|double-stranded P;D D DNAof D M Cgrowth activation ofbasolateral phospholipase plasma actinA2 filament activity membrane|endoplasmic by calcium-mediated reticulum signaling|activation membrane|endosome|extracellular binding|epidermal phospholipase activity|axon space|Golgi factor receptor guidance|cell membrane|int activitp D binding|ATP D;Dbinding|double-stranded P;D D DNAof D M Cgrowth activation ofbasolateral phospholipase plasma actinA2 filament activity membrane|endoplasmic by calcium-mediated reticulum signaling|activation membrane|endosome|extracellular binding|epidermal phospholipase activity|axon space|Golgi factor receptor guidance|cell membrane|int activitp D binding|ATP D;Dbinding|double-stranded D;D D DNAof D M Cgrowth bone maturation|cell integral togrowth|insulin plasma ATP binding|fibroblast membrane receptor signaling growth D;D;D;D;D;D factor pathway|JAK-STAT P;D;D;D;D;D binding|fibroblast growth cascade|negative activity|identical regulation protein of bind dev D D cascade|MAPKKK D factor receptor H bone maturation|cell integral togrowth|insulin plasma ATP binding|fibroblast membrane receptor signaling growth D;D;D;D;D;D factor pathway|JAK-STAT P;D;D;D;D;D binding|fibroblast growth cascade|negative activity|identical regulation protein of bind dev D D cascade|MAPKKK A factor receptor M bone maturation|cell integral togrowth|insulin plasma ATP binding|fibroblast membrane receptor signaling growth factor pathway|JAK-STAT binding|fibroblast growth cascade|negative activity|identical regulation protein of bind dev D D;D;D;D;D D;D;D;P;D D cascade|MAPKKK D factor receptor M bone maturation|cell integral togrowth|insulin plasma ATP binding|fibroblast membrane receptor signaling growth pathway|JAK-STAT binding|fibroblast growth cascade|negative activity|identical regulation protein of bind dev D D;D;D factor D;D;D . cascade|MAPKKK D factor receptor H bone maturation|cell integral togrowth|insulin plasma ATP binding|fibroblast membrane receptor signaling growth factor pathway|JAK-STAT growth cascade|negative activity|identical regulation protein of bind dev D D Pbinding|fibroblast D cascade|MAPKKK D factor receptor M positive regulation integraloftocell plasma ATP proliferation binding|vascular membrane endothelial growth receptor activity D D;D D;D factor D D M connexon complex|integral D to membrane D D D D H actin filament caveola|cytoskeleton|cytosol|endomembrane polymerization|activation ATP binding|growth hormone receptor system|nucleus by binding|heme phosphorylation|activation binding|histone binding|histone kinase activity|blood activity (H3-Y co T of caspase D activity D protein D D Mof JAK2 kinase actin filament caveola|cytoskeleton|cytosol|endomembrane polymerization|activation ATP binding|growth hormone receptor system|nucleus by binding|heme phosphorylation|activation binding|histone binding|histone kinase activity|blood activity (H3-Y co T of caspase D activity D protein D D L of JAK2 kinase male gonadextracellular development|transmembrane ATP space|integral binding|protein receptor binding|receptor tyrosine signaling kinase protein tyrosine kinase activity D to membrane D;D protein D;P D signaling D pathway M male gonadextracellular development|transmembrane ATP space|integral binding|protein receptor binding|receptor protein D;D;D tyrosine signaling kinase protein tyrosine kinase activity D to membrane D;D;D D signaling D pathway M male gonadextracellular development|transmembrane ATP space|integral binding|protein receptor binding|receptor tyrosine signaling kinase protein tyrosine kinase activity T to membrane D;D protein B;D D signaling D pathway L activation ofplasma MAPKKmembrane activity|axon GTP binding|GTPase guidance|blood activity|protein binding D growth factor D P;Pcoagulation|epidermal B;P D receptorHsignaling pathway|insulin recept activation ofplasma MAPKKmembrane activity|axon GTP binding|GTPase guidance|blood activity|protein binding D growth factor D D;Dcoagulation|epidermal D;D D receptorHsignaling pathway|insulin recept activation ofplasma MAPKKmembrane activity|axon GTP binding|GTPase guidance|blood activity|protein binding D growth factor D D;Dcoagulation|epidermal D;D D receptorMsignaling pathway|insulin recept integral to membrane phosphatidate activityD;D;P D phosphatase D;D;D D D M axon guidance|cell basal plasma proliferation ATP membrane|integral binding|hepatocyte toD;D plasma growth factor membrane activity|protein D P;Dreceptor D D binding N mismatch repair|somatic chiasma|MutLalpha ATP hypermutation binding|ATPase complex|MutLbeta activity|protein complex|synaptonemal genes binding D complexD D of immunoglobulin D;D;D P;D;D H mismatch repair|somatic chiasma|MutLalpha ATP hypermutation binding|ATPase complex|MutLbeta activity|protein complex|synaptonemal genes binding D complexD D of immunoglobulin D;D;D D;D;D H mismatch repair|somatic chiasma|MutLalpha ATP hypermutation binding|ATPase complex|MutLbeta activity|protein complex|synaptonemal genes binding D complexD D of immunoglobulin D;D;D D;D;P M mismatch repair|somatic chiasma|MutLalpha ATP hypermutation binding|ATPase complex|MutLbeta activity|protein complex|synaptonemal genes binding D complexA D of immunoglobulin D;D;D;D P;B;P;P M B cell differentiation|DNA MutSalpha complex|MutSbeta ATP damage binding|DNA-dependent response, complex|nuclear signal transduction ATPase chromosome activity|double-strand/single-strand by p53Dclass mediator induction junction of apoptosis|double binding|guanine/ D D;D;D D;D;D D resulting H inDNA B cell differentiation|DNA MutSalpha complex|MutSbeta ATP damage binding|DNA-dependent response, complex|nuclear signal transduction ATPase chromosome activity|double-strand/single-strand by p53Dclass mediator induction junction of apoptosis|double binding|guanine/ D D;D;D D;D;D D resulting H inDNA


B cell differentiation|DNA MutSalpha complex|MutSbeta ATP damage binding|DNA-dependent response, complex|nuclear signal transduction ATPase chromosome activity|double-strand/single-strand by p53Dclass mediator induction junction of apoptosis|double binding|guanine/ D D;D;D D;D;D D resulting H inDNA B cell differentiation|DNA MutSalpha complex|MutSbeta ATP damage binding|DNA-dependent response, complex|nuclear signal transduction ATPase chromosome activity|double-strand/single-strand by p53Dclass mediator induction junction of apoptosis|double binding|guanine/ D D;D;D P;P;P D resulting M inDNA actin cytoskeleton cytoskeleton|early organization|negative cytoskeletal endosome|extrinsic regulation binding|protein D;D;D;D;D;D;D to ofmembrane|filopodium cell migration|negative D;D;D;D;D;D;D binding regulation of cell H proliferation|negative region regulation of cytoplasm o . protein D membrane|nucleolus|perinuclear D actin cytoskeleton cytoskeleton|early organization|negative cytoskeletal endosome|extrinsic regulation binding|protein D;D;D;D;D;D to ofmembrane|filopodium cell migration|negative D;D;P;P;D;P binding regulation of cell M proliferation|negative region regulation of cytoplasm o . protein D membrane|nucleolus|perinuclear D actin cytoskeleton cytoskeleton|early organization|negative cytoskeletal endosome|extrinsic regulation binding|protein D;P;P;D;D;D to ofmembrane|filopodium cell migration|negative P;B;B;D;D;P binding regulation of cell M proliferation|negative region regulation of cytoplasm o . protein D membrane|nucleolus|perinuclear D actin cytoskeleton cytoskeleton|early organization|negative cytoskeletal endosome|extrinsic regulation binding|protein P;D;D;D;D;D;D to ofmembrane|filopodium cell migration|negative P;P;P;P;P;P;P binding regulation of cell M proliferation|negative region regulation of cytoplasm o . protein D membrane|nucleolus|perinuclear D actin cytoskeleton cytoskeleton|early organization|negative cytoskeletal endosome|extrinsic regulation binding|protein D;D;D;D;D;D;D;D to ofmembrane|filopodium cell migration|negative D;P;D;D;D;P;P;P binding regulation of cell L proliferation|negative region regulation of cytoplasm o . protein D membrane|nucleolus|perinuclear D aortic valve cytosol|endoplasmic morphogenesis|immune calcium ion reticulum binding|protein response|negative lumen|extracellular regulation ofactivity BMP lumen|integral to membrane|nucleoplasm|plasma regulation of cell-substrat me D D binding|receptor D region|Golgi D signaling D pathway|negative M aortic valve cytosol|endoplasmic morphogenesis|immune calcium ion reticulum binding|protein response|negative lumen|extracellular regulation ofactivity BMP lumen|integral to membrane|nucleoplasm|plasma regulation of cell-substrat me T D binding|receptor D region|Golgi D signaling D pathway|negative M aortic valve cytosol|endoplasmic morphogenesis|immune calcium ion reticulum binding|protein response|negative lumen|extracellular regulation ofactivity BMP lumen|integral to membrane|nucleoplasm|plasma regulation of cell-substrat me T D binding|receptor D region|Golgi U signaling D pathway|negative M cardiac myofibril cytoplasm|integral assembly|cell ATP binding|platelet-derived to activation|luteinization|metanephric plasma membrane|nucleus factor alpha-receptor glomerular capillary activity|platelet-derived growth factor phosphorylati binding|p D D;D;DgrowthD;D;D U D formation|peptidyl-tyrosine M cardiac myofibril cytoplasm|integral assembly|cell ATP binding|platelet-derived to activation|luteinization|metanephric plasma membrane|nucleus factor alpha-receptor glomerular capillary activity|platelet-derived growth factor phosphorylati binding|p D D;D growthD;D U D formation|peptidyl-tyrosine M cardiac myofibril cytoplasm|integral assembly|cell ATP binding|platelet-derived to activation|luteinization|metanephric plasma membrane|nucleus factor alpha-receptor glomerular capillary activity|platelet-derived growth factor phosphorylati binding|p D D;P growthP;B U D formation|peptidyl-tyrosine M activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntDreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D M activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntDreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D M activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntDreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D H activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntDreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D M activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntDreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D H activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntAreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D H activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntAreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D H activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntDreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D M activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntDreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D M activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntDreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D M activation ofcytosol|internal mitotic anaphase-promoting anaphase-promoting side of plasma complex membrane|PML complex binding|enzyme binding|inositol-1,3,4,5-tetrakisphosphate WntDreceptor signaling pathway|cell 3-phosphatase proliferation|c . D activity|apoptosis|canonical Dbody D M androgen receptor chromatin|PML signaling androgen body|Rb-E2F pathway|cell receptor complex|SWI/SNF cycle binding|DNA binding|kinase remodeling|G1 binding|phosphoprotein phase cell cycle|interspecies interactio DNA b D Darrest|chromatin D complex D D of mitotic Lbinding|sequence-specific homophilic cell integral adhesion|positive to membrane ATP binding|calcium regulation of ionmetanephric binding|transmembrane glomerulusDdevelopment|positive receptor protein tyrosine regulation transcription, DNA-de D D;D;D D;D;D D L kinaseofactivity homophilic cell integral adhesion|positive to membrane ATP binding|calcium regulation of ionmetanephric binding|transmembrane glomerulusDdevelopment|positive receptor protein tyrosine regulation transcription, DNA-de D D;D;D D;D;D D M kinaseofactivity homophilic cell integral adhesion|positive to membrane ATP binding|calcium regulation of ionmetanephric binding|transmembrane glomerulusDdevelopment|positive receptor protein tyrosine regulation transcription, DNA-de D D;D;D D;D;D D H kinaseofactivity homophilic cell integral adhesion|positive to membrane ATP binding|calcium regulation of ionmetanephric binding|transmembrane glomerulusDdevelopment|positive receptor protein tyrosine regulation transcription, DNA-de D D;D;D D;D;D D M kinaseofactivity homophilic cell integral adhesion|positive to membrane ATP binding|calcium regulation of ionmetanephric binding|transmembrane glomerulusDdevelopment|positive receptor protein tyrosine regulation transcription, DNA-de D D;D;D D;D;D D M kinaseofactivity myeloid cellnucleus|nucleus differentiation|negative ATP binding|calcium of binding|DNA granulocyte differentiation|positive binding|DNA binding|protein of angiogenesis|positive heterodimerization regulatio ac Tregulationion D;D;D;D;D D;D;D;D;D D binding|protein Dregulation M myeloid cellnucleus|nucleus differentiation|negative ATP binding|calcium of D;P;P;P;D;D;D binding|DNA granulocyte D;D;D;P;D;D;D differentiation|positive binding|DNA binding|protein of angiogenesis|positive heterodimerization regulatio ac Dregulationion D binding|protein Dregulation M myeloid cellnucleus|nucleus differentiation|negative ATP binding|calcium of binding|DNA granulocyte differentiation|positive binding|DNA binding|protein of angiogenesis|positive heterodimerization regulatio ac Dregulationion D;D;D;D;D D;D;D;D;D D binding|protein Dregulation M activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D Dbinding|chromatin P repair|blood D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision binding|chromatin repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D;D;D;D D;D;D;D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision binding|chromatin repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D;D;D;D D;D;D;D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision binding|chromatin repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D;D;D;D D;D;D;D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision binding|chromatin repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D P;D;P;P B;D;P;B D coagulation|cell A binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision binding|chromatin repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D;D;D;D D;D;D;D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision binding|chromatin repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D;D;D;D D;D;D;D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision binding|chromatin repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D;P;D;D D;P;D;D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;D;D;D;D;D binding|chromatin D;P;D;D;D;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision B;B;B;B;B;D binding|chromatin B;B;B;P;B;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;D;D;D;D;D;D binding|chromatin D;D;D;D;D;D;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;P;D;D;P;P;P binding|chromatin D;P;D;D;P;P;P repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;D;D;D;D;D;D binding|chromatin D;D;D;D;D;D;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D N coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;P;D;D;P;B;D binding|chromatin D;B;D;D;B;B;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell A binding|damaged Marrest|cell

activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;D;D;D;D;D;D binding|chromatin D;D;D;D;D;D;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;D;D;D;D;D;D binding|chromatin D;D;D;D;D;D;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;D;D;D;D;D;D binding|chromatin D;D;P;D;D;D;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;D;D;D;D;D;D binding|chromatin D;D;D;D;D;D;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;D;D;D;D;D;D binding|chromatin D;D;D;P;D;D;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell activation ofcytoplasm|cytosol|endoplasmic caspase activity ATP binding|chaperone by cytochrome reticulum|insoluble c|base-excision D;D;D;P;D;D;D binding|chromatin D;D;D;P;D;D;D repair|blood fraction|mitochondrion|nuclear binding|copper ion cyclechromatin|nuclear DNA differentiation|cell binding|DNA matrix|nucleolu strand prol D D coagulation|cell D binding|damaged Marrest|cell anti-apoptosis|cell cytosol|endoplasmic morphogenesis|negative protein binding|transcription reticulum|membrane|mitochondrion|nucleus regulation of cell binding proliferation|negative regulation ofL transcription from RNA polymera D P;D factor P;P D D anti-apoptosis|cell cytosol|endoplasmic morphogenesis|negative protein binding|transcription reticulum|membrane|mitochondrion|nucleus regulation of cell binding regulation ofL transcription from RNA polymera T D factor D proliferation|negative D D



FATHMM_pred RadialSVM_pred COSMIC_fusion_genes COSMIC_tissue_types_affected COSMIC_total_alterations_in_gene Tumorscape_Amplification_Peaks Tumorscape_Deletion_Peaks LR_pred COSMIC_overlapping_mutations haematopoietic_and_lymphoid_tissue(807)|lung(5)|stomach(2)|centra all_hematologic(13;0.0361)|Acute D;D D T p.G250E(72) 817 large_intestine(2123)|stomach(123)|soft_tissue(55)|small_intestine(3 all_cancers(142;3.01e-27)|all_epi T;T;T;T;T D D p.?(1) 2515 p.P1369fs*5(1)|p.K1192fs*3(1)|p.?(1)|p.P1369H(1) large_intestine(2123)|stomach(123)|soft_tissue(55)|small_intestine(3 all_cancers(142;3.01e-27)|all_epi D;D;D D D 2515 p.P1420L(2)|p.P1420fs*2(1)|p.Y1376fs*41(1)|p.?(1)|p.S1411fs*41(1)|p.K1192fs*3(1)|p.S1421 large_intestine(2123)|stomach(123)|soft_tissue(55)|small_intestine(3 all_cancers(142;3.01e-27)|all_epi D;D;D D D 2515 p.L1482fs*25(1)|p.K1454fs*3(1)|p.L1482F(1)|p.K1192fs*3(1)|p.?(1) large_intestine(2123)|stomach(123)|soft_tissue(55)|small_intestine(3 all_cancers(142;3.01e-27)|all_epi D;D;D D D 2515 all_cancers(142;3.01e-27)|all_epi D;D;D D D p.K1192fs*3(1)|p.?(1) large_intestine(2123)|stomach(123)|soft_tissue(55)|small_intestine(3 2515 p.V471F(3) KIAA1549/BRAF(229)|AKAP9_ENST00000356239/BRAF(10)|AGTRAP/BRAF(2 thyroid(8166)|large_intestine(5052)|skin(3798)|NS(368)|central_nervo D D D 18290 Melanoma(164;0.00956) p.G464E(7)|p.G464V(7)|p.G464R(1) KIAA1549/BRAF(229)|AKAP9_ENST00000356239/BRAF(10)|AGTRAP/BRAF(2 thyroid(8166)|large_intestine(5052)|skin(3798)|NS(368)|central_nervo D D D 18290 Melanoma(164;0.00956) breast(148)|stomach(71)|biliary_tract(8)|endometrium(3)|soft_tissue(2 all_neural(199;0.0189)|Ovarian(13 T;T D D p.V157_Q177del(1) 243 p.Y380_K440del(5)|p.T399fs*17(3)|p.D400del(1)|p.D400Y(1) breast(148)|stomach(71)|biliary_tract(8)|endometrium(3)|soft_tissue(2 all_neural(199;0.0189)|Ovarian(13 T D D 243 breast(148)|stomach(71)|biliary_tract(8)|endometrium(3)|soft_tissue(2 all_neural(199;0.0189)|Ovarian(13 T;T D D p.E682fs*34(1) 243 p.0?(1112)|p.?(23)|p.L32_L37del(6)|p.G35E(3)|p.G35R(2)|p.G35fs*13(1)|p.V28_V51del(1)|p. haematopoietic_and_lymphoid_tissue(647)|skin(419)|upper_aerodige all_cancers(5;0)|Acute lymphobla D;D D D 3678 haematopoietic_and_lymphoid_tissue(38)|lung(6)|central_nervous_s D D D 54 ermal growth factor receptor activity|identical protein p.E746_A750del(1613)|p.L747_P753>S(110)|p.L747_A750>P(74)|p.E746_S752>V(67)|p.L7 binding|MAP/ERK kinase lung(9213)|central_nervous_system(103)|stomach(41)|upper_aerodig kinase activity|protein heterodimerization activity|protein phosp 9571 all_cancers(1;1.57e-46)|all_epithelial(1;5.62e p.S768I(53)|p.S768_V769insAWT(1)|p.S768N(1)|p.S752_V769del(1)|p.S768_V769insVAS(1 lung(9213)|central_nervous_system(103)|stomach(41)|upper_aerodig D;D;D D D 9571 all_cancers(1;1.57e-46)|all_epithelial(1;5.62e p.H773_V774insNPH(12)|p.V774_C775insHV(4)|p.H773_V774insPH(3)|p.H773_V774insH(3 lung(9213)|central_nervous_system(103)|stomach(41)|upper_aerodig T;T;T D D 9571 all_cancers(1;1.57e-46)|all_epithelial(1;5.62e p.G779S(4)|p.G779F(3)|p.G779C(1) lung(9213)|central_nervous_system(103)|stomach(41)|upper_aerodig D;D;D D D 9571 all_cancers(1;1.57e-46)|all_epithelial(1;5.62e p.R831C(4)|p.R831H(3)lung(9213)|central_nervous_system(103)|stomach(41)|upper_aerodig D;D;D D D 9571 all_cancers(1;1.57e-46)|all_epithelial(1;5.62e p.V834L(5)|p.V834A(3)|p.V834M(1)|p.V834del(1) lung(9213)|central_nervous_system(103)|stomach(41)|upper_aerodig D;D;D D D 9571 all_cancers(1;1.57e-46)|all_epithelial(1;5.62e p.L858R(3429)|p.L858L(4)|p.L858M(4)|p.L858Q(3)|p.L858A(2)|p.L858W(1)|p.L858P(1)|p.L85 lung(9213)|central_nervous_system(103)|stomach(41)|upper_aerodig D;D;D D D 9571 all_cancers(1;1.57e-46)|all_epithelial(1;5.62e p.L858R(3429)|p.L858L(4)|p.L858M(4)|p.L858Q(3)|p.L858A(2)|p.L858W(1)|p.L858P(1)|p.L85 lung(9213)|central_nervous_system(103)|stomach(41)|upper_aerodig D;D;D D D 9571 all_cancers(1;1.57e-46)|all_epithelial(1;5.62e D;D;D;D;D;D;D urinary_tract(2177)|skin(314)|upper_aerodigestive_tract(57)|haemato Breast(71;0.212)|all_epithelial(65; D D p.C228R(1) 2600 D;T;T;T;T;T;T p.S249C(1368)|p.R248_S249insC(2)|p.S249T(1)|p.R248_S249del(1) urinary_tract(2177)|skin(314)|upper_aerodigestive_tract(57)|haemato Breast(71;0.212)|all_epithelial(65; D D 2600 T;T;T;D;T;DD urinary_tract(2177)|skin(314)|upper_aerodigestive_tract(57)|haemato Breast(71;0.212)|all_epithelial(65; D 2600 urinary_tract(2177)|skin(314)|upper_aerodigestive_tract(57)|haemato Breast(71;0.212)|all_epithelial(65; D;D;D;D;D D D 2600 urinary_tract(2177)|skin(314)|upper_aerodigestive_tract(57)|haemato Breast(71;0.212)|all_epithelial(65; T D D 2600 Lung SC(185;0.0156)|Ovarian(18 leukemia(6;0.04) D;D;D D D p.G617_S618ins21(1) haematopoietic_and_lymphoid_tissue(8536)|lung(7)|ovary(3)|stomac 8549 Acute lymphoblastic D D D ovary(1) 1 Esophageal squamous(72;0.0166)|Lung NSC p.R564L(3)|p.R564Q(2) PCM1/JAK2(30)|PAX5/JAK2(18)|ETV6/JAK2(11)|BCR/JAK2(6)|SSBP2/JAK2(4)| haematopoietic_and_lymphoid_tissue(28629)|lung(5)|breast(5)|ovary Acute lymphoblastic leukemia(23; D;D;D D D 28641 all_hematologic(13;0.137) haematopoietic_and_lymphoid_tissue(28629)|lung(5)|breast(5)|ovary Acute lymphoblastic leukemia(23; D;D;D D D p.S591L(1) PCM1/JAK2(30)|PAX5/JAK2(18)|ETV6/JAK2(11)|BCR/JAK2(6)|SSBP2/JAK2(4)| 28641 all_hematologic(13;0.137) p.K550_K558del(33)|p.P551_E554del(14)|p.P551_V555del(12)|p.K550_E554del(10)|p.P551 soft_tissue(3273)|haematopoietic_and_lymphoid_tissue(1572)|skin(9 D;D D D 5118 all_cancers(7;0.00453)|all_lung(4;0.000565)|L p.V560_L576del(22)|p.N564_L576del(13)|p.K558_G565>R(11)|p.V559_G565del(11)|p.K558 soft_tissue(3273)|haematopoietic_and_lymphoid_tissue(1572)|skin(9 D;D D D 5118 all_cancers(7;0.00453)|all_lung(4;0.000565)|L soft_tissue(3273)|haematopoietic_and_lymphoid_tissue(1572)|skin(9 D;D D D 5118 all_cancers(7;0.00453)|all_lung(4;0.000565)|L p.A59T(8)|p.A59E(3)|p.A59G(2) large_intestine(12391)|pancreas(3285)|lung(2847)|biliary_tract(521)|o D;D D D 21052 all_cancers(2;1e-35)|all_epithelial(2;1.97e-38 large_intestine(12391)|pancreas(3285)|lung(2847)|biliary_tract(521)|o D;T;T;T D D p.P34S(1) 21052 all_cancers(2;1e-35)|all_epithelial(2;1.97e-38 p.G12D(7175)|p.G12V(4780)|p.G12C(2482)|p.G12A(1180)|p.G12S(1119)|p.G12R(691)|p.G1 large_intestine(12391)|pancreas(3285)|lung(2847)|biliary_tract(521)|o T;T;T;T D D 21052 all_cancers(2;1e-35)|all_epithelial(2;1.97e-38 D;D T T 0 upper_aerodigestive_tract(63)|lung(41)|kidney(18)|NS(10)|ovary(5)|th Ovarian(593;0.133) D;D;D D D 159 all_cancers(3;1.25e-07)|all_epithelial(6;4.07e large_intestine(40)|haematopoietic_and_lymphoid_tissue(8)|ovary(6) D;D;T D D p.0?(1)|p.E172K(1) 77 D;D;D;D;D;D;D large_intestine(40)|haematopoietic_and_lymphoid_tissue(8)|ovary(6) D D p.0?(1) 77 D;D;D;D;D;D large_intestine(40)|haematopoietic_and_lymphoid_tissue(8)|ovary(6) D D p.0?(1) 77 D;D;D;D;D;D p.A681V(1)|p.K678fs*11(1)|p.0?(1) large_intestine(40)|haematopoietic_and_lymphoid_tissue(8)|ovary(6) D D 77 large_intestine(33)|haematopoietic_and_lymphoid_tissue(6)|endome all_hematologic(82;0.0359)|Acute D;D;D D D p.?(2) 55 large_intestine(33)|haematopoietic_and_lymphoid_tissue(6)|endome all_hematologic(82;0.0359)|Acute D;D;D D D p.?(2) 55

large_intestine(33)|haematopoietic_and_lymphoid_tissue(6)|endome all_hematologic(82;0.0359)|Acute p.?(2) 55 p.?(2)|p.C822F(1)|p.C822*(1) large_intestine(33)|haematopoietic_and_lymphoid_tissue(6)|endome all_hematologic(82;0.0359)|Acute 55 p.V122_K149del(5)|p.L127_D382del(1)|p.L127_P134del(1)|p.K123fs*2(1)|p.V110_L141del(1 meninges(372)|soft_tissue(284)|central_nervous_system(20)|kidney( 728 p.R196*(12)|p.L127_D382del(1)|p.L140_P252del(1)|p.?(1) meninges(372)|soft_tissue(284)|central_nervous_system(20)|kidney( 728 p.R341*(20)|p.M334fs*4(1)|p.?(1)|p.E342fs*1(1)|p.M334_Q362del(1)|p.L127_D382del(1)|p.E meninges(372)|soft_tissue(284)|central_nervous_system(20)|kidney( 728 p.L127_D382del(1)|p.?(1) meninges(372)|soft_tissue(284)|central_nervous_system(20)|kidney( 728 p.M375fs*20(1)|p.?(1) meninges(372)|soft_tissue(284)|central_nervous_system(20)|kidney( 728 p.T2512fs*1(1)|p.L2511L(1)|p.E2507fs*6(1) haematopoietic_and_lymphoid_tissue(791)|upper_aerodigestive_trac Myeloproliferative disorder(178;0. 856 all_cancers(76;0.223) p.E2507fs*6(1)|p.F2510fs*1(1) haematopoietic_and_lymphoid_tissue(791)|upper_aerodigestive_trac Myeloproliferative disorder(178;0. 856 all_cancers(76;0.223) p.L1594P(34)|p.R1595_E1596ins12(3)|p.R1595>PRLPHNSSFHFLR(3)|p.F1593_L1594ins1 haematopoietic_and_lymphoid_tissue(791)|upper_aerodigestive_trac Myeloproliferative disorder(178;0. 856 all_cancers(76;0.223) soft_tissue(572)|small_intestine(40)|stomach(16)|lung(16)|central_ne 674 all_cancers(7;0.000425)|all_lung(4;0.000343) p.S566_E571>R(44)|p.S566_E571>K(8)|p.S566_E571>RIQ(1)|p.S566_E571>IRIQ(1)|p.S56 soft_tissue(572)|small_intestine(40)|stomach(16)|lung(16)|central_ne 674 all_cancers(7;0.000425)|all_lung(4;0.000343) soft_tissue(572)|small_intestine(40)|stomach(16)|lung(16)|central_ne p.P589S(1) 674 all_cancers(7;0.000425)|all_lung(4;0.000343) p.?(4)|p.Y27fs*1(3)|p.Y27_N212>Y(2)|p.P30fs*24(1) endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.C105F(6)|p.C105W(4)|p.R55fs*1(4)|p.C105S(3)|p.?(2)|p.Y27fs*1(2)|p.C105Y(2)|p.Y27_N2 endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.H123Y(4)|p.R55fs*1(4)|p.I122fs*2(3)|p.?(2)|p.Y27fs*1(2)|p.Y27_N212>Y(2)|p.A121_F145d endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.A126T(5)|p.R55fs*1(4)|p.A126D(3)|p.?(2)|p.Y27fs*1(2)|p.A126P(2)|p.Y27_N212>Y(2)|p.A1 endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.R55fs*1(4)|p.G127E(3)|p.?(2)|p.Y27fs*1(2)|p.Y27_N212>Y(2)|p.A121_F145del(1)|p.G127fs endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.G129R(6)|p.R55fs*1(4)|p.G129*(3)|p.K128_R130del(3)|p.?(2)|p.Y27fs*1(2)|p.Y27_N212>Y endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.R130G(65)|p.R130*(61)|p.R130Q(43)|p.R130fs*4(12)|p.R130L(7)|p.R55fs*1(4)|p.R130P(4) endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.R55fs*1(4)|p.?(2)|p.V133I(2)|p.Y27fs*1(2)|p.Y27_N212>Y(2)|p.A121_F145del(1)|p.T131fs* endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.R55fs*1(4)|p.N212fs*1(2)|p.Y27fs*1(2)|p.G165_*404del(1)|p.S227F(1)|p.?(1)|p.G165_K342 endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.R55fs*1(4)|p.G251C(4)|p.N212fs*1(2)|p.Y27fs*1(2)|p.G165_*404del(1)|p.?(1)|p.G165_K34 endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 p.R55fs*1(4)|p.?(2)|p.N212fs*1(2)|p.Y27fs*1(2)|p.P339S(2)|p.G165_*404del(1)|p.P339L(1)|p endometrium(831)|central_nervous_system(657)|skin(121)|haematop all_cancers(4;3.61e-31)|all_epithe 2334 lung(94)|eye(89)|central_nervous_system(47)|bone(22)|breast(21)|ur all_cancers(8;6.9e-71)|all_epitheli p.?(7)|p.R798W(1) 358 thyroid(404)|adrenal_gland(20)|lung(9)|large_intestine(5)|breast(4)|ov Ovarian(717;0.0423) 451 thyroid(404)|adrenal_gland(20)|lung(9)|large_intestine(5)|breast(4)|ov Ovarian(717;0.0423) 451 thyroid(404)|adrenal_gland(20)|lung(9)|large_intestine(5)|breast(4)|ov Ovarian(717;0.0423) 451 thyroid(404)|adrenal_gland(20)|lung(9)|large_intestine(5)|breast(4)|ov Ovarian(717;0.0423) 451 thyroid(404)|adrenal_gland(20)|lung(9)|large_intestine(5)|breast(4)|ov Ovarian(717;0.0423) 451 p.E223G(1)|p.R250H(1)haematopoietic_and_lymphoid_tissue(383)|lung(2)|ovary(1)|central_n 387 p.G135_N136insG(1)|p.N159fs*49(1)|p.R162K(1) haematopoietic_and_lymphoid_tissue(383)|lung(2)|ovary(1)|central_n 387 haematopoietic_and_lymphoid_tissue(383)|lung(2)|ovary(1)|central_n p.L112fs*24(1) 387 p.0?(7)|p.A347T(2)|p.L344fs*22(1)|p.A347G(1)|p.?(1)|p.I332fs*5(1) large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.R280T(53)|p.R280K(41)|p.R280G(18)|p.R280S(13)|p.R280I(12)|p.R280*(8)|p.R280fs*65(7 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.C277F(20)|p.C277Y(15)|p.0?(7)|p.C277*(6)|p.C277G(4)|p.C277C(4)|p.?(2)|p.C277W(2)|p.C large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.A276P(13)|p.A276S(9)|p.0?(7)|p.A276V(7)|p.A276T(7)|p.A276D(6)|p.A276G(4)|p.?(2)|p.A2 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.R273H(469)|p.R273C(394)|p.R273L(83)|p.R273P(24)|p.R273S(11)|p.R273G(9)|p.0?(7)|p.R large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.E271K(22)|p.E271*(14)|p.0?(7)|p.E271V(5)|p.E271Q(3)|p.E271G(3)|p.E271D(3)|p.?(2)|p.G large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.0?(7)|p.S269N(4)|p.S269C(4)|p.S269S(3)|p.S269G(3)|p.?(2)|p.G266_E271delGRNSFE(2) large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.G262V(11)|p.0?(7)|p.G262D(4)|p.G262fs*83(4)|p.?(3)|p.G262_F270delGNLLGRNSF(2)|p. large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.0?(7)|p.T230I(7)|p.T230P(2)|p.T230fs*6(2)|p.T230N(2)|p.T230S(2)|p.C229_H233delCTTIH large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.0?(7)|p.T230I(7)|p.T230P(2)|p.T230fs*6(2)|p.T230N(2)|p.T230S(2)|p.C229_H233delCTTIH large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.Y220C(201)|p.Y220N(12)|p.Y220H(9)|p.Y220S(9)|p.0?(7)|p.Y220fs*27(4)|p.Y220*(3)|p.Y22 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.D208V(12)|p.0?(7)|p.D208E(5)|p.D208G(3)|p.D207fs*6(2)|p.D208N(2)|p.D208fs*1(1)|p.K16 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.0?(7)|p.P191del(5)|p.A189_V197delAPPQHLIRV(4)|p.P191fs*56(3)|p.P191L(2)|p.P191fs*5 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.R175H(729)|p.R175L(19)|p.R175C(12)|p.R175G(11)|p.0?(7)|p.R175P(5)|p.R175S(5)|p.R43 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 Downloaded from http://annonc.oxfordjournals.org/ by guest on December 26, 2016

D;D;D D D D;D;D D D D;D;D;D;D;D;D;D;D;D;D D D T;T;T;T;T;T;T;T;T D D D;D;D;D;D;D;D;D D D D;D;D;D;D;D;D;D;D D D D;D;D;D;D;D;D;D;D D D D D D T D D D D D T;T;T;T D D D D D D;D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D D;D D D D;D D D D;D D D D;D D D D;D D D T;T;T;T;D;DD D D;D;D;D;D;D;D;D D D D;D;D;D;D;D;D;D;D D D D;D D D D;D;D;D;D;D D D D;D;D;D;D;D D D D;D;D;D;D;D D D D;D;D;D;D;D D D D;D;D;D;D;D D D D;D;D;D;D;D D D D;D;D;D;D;D D D D;D;D;D;D;D;D;D D D D;D;D;D;D;D;D;D D D D;D;D;D;D;D;D;D D D D;D;D;D;D;D;D;D D D D;D;D;D;D;D;D;D D D D;D;D;D;D;D;D;D D D

D;D;D;D;D;D;D;D D D;D;D;D;D;D;D;D;D D D;D;D;D;D;D;D;D;D D D;D;D;D;D;D;D;D D D;D;D;D;D;D;D;D D D;D;D;D;D;D;D;D D D;D D D D

D D D D D D D D

p.E171*(10)|p.E171K(8)|p.0?(7)|p.E171Q(3)|p.E171G(3)|p.E171fs*10(3)|p.E171fs*3(2)|p.E17 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.C141Y(61)|p.C141*(11)|p.C141R(10)|p.C141W(10)|p.0?(7)|p.C141C(4)|p.C141F(4)|p.C141 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.A138V(17)|p.A138P(13)|p.0?(7)|p.A138fs*32(5)|p.A138T(4)|p.A138fs*11(3)|p.N131fs*27(2 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.L130V(11)|p.L130F(7)|p.L130R(7)|p.0?(7)|p.Y126_K132delYSPALNK(6)|p.L130L(4)|p.L13 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.T125T(15)|p.0?(7)|p.T125M(7)|p.T125R(3)|p.T125K(3)|p.G59fs*23(3)|p.V73fs*9(1)|p.T125P large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.0?(7)|p.T118fs*5(4)|p.T118I(3)|p.G59fs*23(3)|p.V73fs*9(1)|p.T118T(1)|p.T118fs*31(1)|p.G1 large_intestine(4656)|breast(2429)|upper_aerodigestive_tract(2212)|l all_cancers(10;1.01e-06)|Myelopr 22245 p.V74D(4)|p.V74fs*85(2)|p.V74A(1)|p.S72_V87>L(1)|p.P71fs*84(1)|p.R60fs*35(1)|p.N67_V7 kidney(1273)|soft_tissue(24)|adrenal_gland(15)|large_intestine(13)|p 1346 p.G144fs*14(5)|p.G144fs*15(4)|p.G144*(3)|p.G144A(1)|p.G144fs*19(1) kidney(1273)|soft_tissue(24)|adrenal_gland(15)|large_intestine(13)|p 1346



TCGAscape_Amplification_Peaks TCGAscape_Deletion_Peaks CCLE_ONCOMAP_total_mutations_in_gene CGC_Mutation_Type CGC_Translocation_Partner CGC_Tumor_Types_Somatic CGC_Tumor_Types_Germline DrugBank CCLE_ONCOMAP_overlapping_mutations all_hematologic(13;0.0361)|Acute OV - Ovarian lymphoblastic Adenosine serous cystadenocarcinoma(145;5.4e-05) triphosphate(DB00171)|Dasatinib(DB01254)|Imatinib(DB00619) leukemia(5;0.0543)|Myeloproliferative BCR|ETV6|NUP214 disorder(178;0.204) T|Mis CML|ALL|T-ALL all_cancers(142;3.01e-27)|all_epithelial(76;2.3e-18)|all_hematologic(541;4.32e-09)|Ovarian(225;1.78e-06)|Lung OV - Ovarian serous cystadenocarcinoma(64;1.09e-113)|Epithelial(69;3.79e-112)|all colorectal|pancreatic|desmoid|hepatoblastom colorectal|pancreatic|desmoid|hep cancers(49;1.67e-104)|BRCA NSC(167;0.000195)|Breast12 D|Mis|N|F|S all_cancers(142;3.01e-27)|all_epithelial(76;2.3e-18)|all_hematologic(541;4.32e-09)|Ovarian(225;1.78e-06)|Lung OV - Ovarian serous cystadenocarcinoma(64;1.09e-113)|Epithelial(69;3.79e-112)|all colorectal|pancreatic|desmoid|hepatoblastom colorectal|pancreatic|desmoid|hep cancers(49;1.67e-104)|BRCA NSC(167;0.000195)|Breast12 D|Mis|N|F|S all_cancers(142;3.01e-27)|all_epithelial(76;2.3e-18)|all_hematologic(541;4.32e-09)|Ovarian(225;1.78e-06)|Lung OV - Ovarian serous cystadenocarcinoma(64;1.09e-113)|Epithelial(69;3.79e-112)|all colorectal|pancreatic|desmoid|hepatoblastom colorectal|pancreatic|desmoid|hep cancers(49;1.67e-104)|BRCA NSC(167;0.000195)|Breast12 D|Mis|N|F|S all_cancers(142;3.01e-27)|all_epithelial(76;2.3e-18)|all_hematologic(541;4.32e-09)|Ovarian(225;1.78e-06)|Lung OV - Ovarian serous cystadenocarcinoma(64;1.09e-113)|Epithelial(69;3.79e-112)|all colorectal|pancreatic|desmoid|hepatoblastom colorectal|pancreatic|desmoid|hep cancers(49;1.67e-104)|BRCA NSC(167;0.000195)|Breast12 D|Mis|N|F|S all_cancers(142;3.01e-27)|all_epithelial(76;2.3e-18)|all_hematologic(541;4.32e-09)|Ovarian(225;1.78e-06)|Lung OV - Ovarian serous cystadenocarcinoma(64;1.09e-113)|Epithelial(69;3.79e-112)|all colorectal|pancreatic|desmoid|hepatoblastom colorectal|pancreatic|desmoid|hep cancers(49;1.67e-104)|BRCA NSC(167;0.000195)|Breast12 D|Mis|N|F|S 164;0.00956) AKAP9|KIAA1549 melanoma|colorectal|papillary thyroid|borderli Sorafenib(DB00398) 61 Mis|T|O 164;0.00956) AKAP9|KIAA1549 melanoma|colorectal|papillary thyroid|borderli Sorafenib(DB00398) 61 Mis|T|O all_neural(199;0.0189)|Ovarian(137;0.0563) Epithelial(162;8.44e-05)|all cancers(182;0.000404)|OV - Ovarian serous lobular cystadenocarcinoma(108;0.000426)|BRCA breast|gastric Mis|N|F|S gastric all_neural(199;0.0189)|Ovarian(137;0.0563) Epithelial(162;8.44e-05)|all cancers(182;0.000404)|OV - Ovarian serous lobular cystadenocarcinoma(108;0.000426)|BRCA breast|gastric Mis|N|F|S gastric all_neural(199;0.0189)|Ovarian(137;0.0563) Epithelial(162;8.44e-05)|all cancers(182;0.000404)|OV - Ovarian serous lobular cystadenocarcinoma(108;0.000426)|BRCA breast|gastric Mis|N|F|S gastric all_cancers(5;0)|Acute lymphoblastic all cancers(2;0)|GBM leukemia(3;0)|all_hematologic(3;0)|all_epithelial(2;2.37e-290)|Lung - Glioblastoma multiforme(3;0)|Lung(2;4.07e-74)|Epithelial(2;1.08e-61)|LUSC NSC(2;1.26e-139)|all_lung(2;4.48e - Lung squamou 17 KIRC - Kidney renal clear cell carcinoma(527;0.000962)|Kidney(363;0.00147) Imatinib(DB00619)|Sunitinib(DB01268) GBM - Glioblastoma multiforme(1;0)|all Cetuximab(DB00002)|Erlotinib(DB00530)|Gefitinib(DB00317)|Lapatinib(DB01259)|Lidocaine(DB00281)| E746_A750del(NCIH1650_LUNG)|E746K(HCC827_LUNG)|E746_A750del(PC14_LUNG)|L7 cancers(1;2.19e-314)|Lung(13;4.65e-05)|LUSC glioma|NSCLC - LungNSCLC squamous cell carcinoma(13;0.00 8 A|O|Mis GBM - Glioblastoma multiforme(1;0)|all Cetuximab(DB00002)|Erlotinib(DB00530)|Gefitinib(DB00317)|Lapatinib(DB01259)|Lidocaine(DB00281)| cancers(1;2.19e-314)|Lung(13;4.65e-05)|LUSC glioma|NSCLC - LungNSCLC squamous cell carcinoma(13;0.00 8 A|O|Mis GBM - Glioblastoma multiforme(1;0)|all Cetuximab(DB00002)|Erlotinib(DB00530)|Gefitinib(DB00317)|Lapatinib(DB01259)|Lidocaine(DB00281)| cancers(1;2.19e-314)|Lung(13;4.65e-05)|LUSC glioma|NSCLC - LungNSCLC squamous cell carcinoma(13;0.00 8 A|O|Mis GBM - Glioblastoma multiforme(1;0)|all Cetuximab(DB00002)|Erlotinib(DB00530)|Gefitinib(DB00317)|Lapatinib(DB01259)|Lidocaine(DB00281)| cancers(1;2.19e-314)|Lung(13;4.65e-05)|LUSC glioma|NSCLC - LungNSCLC squamous cell carcinoma(13;0.00 8 A|O|Mis GBM - Glioblastoma multiforme(1;0)|all Cetuximab(DB00002)|Erlotinib(DB00530)|Gefitinib(DB00317)|Lapatinib(DB01259)|Lidocaine(DB00281)| cancers(1;2.19e-314)|Lung(13;4.65e-05)|LUSC glioma|NSCLC - LungNSCLC squamous cell carcinoma(13;0.00 8 A|O|Mis GBM - Glioblastoma multiforme(1;0)|all Cetuximab(DB00002)|Erlotinib(DB00530)|Gefitinib(DB00317)|Lapatinib(DB01259)|Lidocaine(DB00281)| cancers(1;2.19e-314)|Lung(13;4.65e-05)|LUSC glioma|NSCLC - LungNSCLC squamous cell carcinoma(13;0.00 8 A|O|Mis GBM - Glioblastoma multiforme(1;0)|all Cetuximab(DB00002)|Erlotinib(DB00530)|Gefitinib(DB00317)|Lapatinib(DB01259)|Lidocaine(DB00281)| cancers(1;2.19e-314)|Lung(13;4.65e-05)|LUSC glioma|NSCLC - LungNSCLC squamous cell carcinoma(13;0.00 8 A|O|Mis GBM - Glioblastoma multiforme(1;0)|all Cetuximab(DB00002)|Erlotinib(DB00530)|Gefitinib(DB00317)|Lapatinib(DB01259)|Lidocaine(DB00281)| L858R(NCIH1975_LUNG) cancers(1;2.19e-314)|Lung(13;4.65e-05)|LUSC glioma|NSCLC - LungNSCLC squamous cell carcinoma(13;0.00 8 A|O|Mis all cancers(2;0.000145)|OV - Ovarian serous cystadenocarcinoma(23;0.0019)|Epithelial(3;0.00221)|GBM IGH@|ETV6bladder|MM|T-cell lymphoma - Glioblastoma multifo Palifermin(DB00039) 1 Mis|T all cancers(2;0.000145)|OV - Ovarian serous cystadenocarcinoma(23;0.0019)|Epithelial(3;0.00221)|GBM IGH@|ETV6bladder|MM|T-cell lymphoma - Glioblastoma multifo Palifermin(DB00039) 1 Mis|T all cancers(2;0.000145)|OV - Ovarian serous cystadenocarcinoma(23;0.0019)|Epithelial(3;0.00221)|GBM IGH@|ETV6bladder|MM|T-cell lymphoma - Glioblastoma multifo Palifermin(DB00039) 1 Mis|T all cancers(2;0.000145)|OV - Ovarian serous cystadenocarcinoma(23;0.0019)|Epithelial(3;0.00221)|GBM IGH@|ETV6bladder|MM|T-cell lymphoma - Glioblastoma multifo Palifermin(DB00039) 1 Mis|T all cancers(2;0.000145)|OV - Ovarian serous cystadenocarcinoma(23;0.0019)|Epithelial(3;0.00221)|GBM IGH@|ETV6bladder|MM|T-cell lymphoma - Glioblastoma multifo Palifermin(DB00039) 1 Mis|T Colorectal(13;0.000157)|READ OV - Ovarian Sorafenib(DB00398)|Sunitinib(DB01268) serous- cystadenocarcinoma(117;0.00154)|all Rectum adenocarcinoma(15;0.105) cancers(112;0.00459)|GBM - Glioblastoma multiforme(1 Mis|O AML|ALL l squamous(72;0.0166)|Lung NSC(181;0.0211)|all_lung(186;0.0323) Acute lymphoblastic leukemia(23;0.0198)|Breast(48;0.147) GBM - Glioblastoma multiforme(50;0.0237)|Lung(218;0.133) ETV6|PCM1|BCR 1 T|Mis|O ALL|AML|MPD| CML Acute lymphoblastic leukemia(23;0.0198)|Breast(48;0.147) GBM - Glioblastoma multiforme(50;0.0237)|Lung(218;0.133) ETV6|PCM1|BCR 1 T|Mis|O ALL|AML|MPD| CML LUSC - Lung Colorectal(1;0.0276)|COAD squamousDasatinib(DB01254)|Imatinib(DB00619)|Sorafenib(DB00398)|Sunitinib(DB01268) cell carcinoma(32;0.000276)|Epithelial(7;0.209) - Colon adenocarcinoma(1;0.171) GIST|AML|TGCT|mastocytosis|mucosal GIST|epithelioma mela 1 Mis|O LUSC - Lung Colorectal(1;0.0276)|COAD squamousDasatinib(DB01254)|Imatinib(DB00619)|Sorafenib(DB00398)|Sunitinib(DB01268) cell carcinoma(32;0.000276)|Epithelial(7;0.209) - Colon adenocarcinoma(1;0.171) GIST|AML|TGCT|mastocytosis|mucosal GIST|epithelioma mela 1 Mis|O LUSC - Lung Colorectal(1;0.0276)|COAD squamousDasatinib(DB01254)|Imatinib(DB00619)|Sorafenib(DB00398)|Sunitinib(DB01268) cell carcinoma(32;0.000276)|Epithelial(7;0.209) - Colon adenocarcinoma(1;0.171) GIST|AML|TGCT|mastocytosis|mucosal GIST|epithelioma mela 1 Mis|O OV - Ovarian serous cystadenocarcinoma(3;1.23e-21)|Epithelial(3;1.31e-20)|all A59T(143B_BONE)119 Mis cancers(3;5.45e-18)|STAD pancreatic|colorectal|lung|thyroid|AML|others - Stomach adenocar OV - Ovarian serous cystadenocarcinoma(3;1.23e-21)|Epithelial(3;1.31e-20)|all cancers(3;5.45e-18)|STAD pancreatic|colorectal|lung|thyroid|AML|others - Stomach adenocar 119 Mis OV - Ovarian serous cystadenocarcinoma(3;1.23e-21)|Epithelial(3;1.31e-20)|all G12D(HPAC_PANCREAS)|G12V(SW403_LARGE_INTESTINE)|G12D(HPAFII_PANCREAS cancers(3;5.45e-18)|STAD pancreatic|colorectal|lung|thyroid|AML|others - Stomach adenocar 119 Mis

GBM - Glioblastoma multiforme(2;2.31e-07)|all cancers(2;0.000419)|STAD - Stomach papillary adenocarcinoma(10;0.000512) renal|head-neck papillary renalsquamous cell Mis colorectal|endometrial|ovarian|CNS colorectal|endometrial|ovarian|CN 1 D|Mis|N|F|S colorectal|endometrial|ovarian|CNS colorectal|endometrial|ovarian|CN 1 D|Mis|N|F|S colorectal|endometrial|ovarian|CNS colorectal|endometrial|ovarian|CN 1 D|Mis|N|F|S colorectal|endometrial|ovarian|CNS colorectal|endometrial|ovarian|CN 1 D|Mis|N|F|S Lung(47;0.101)|LUSC - Lung squamous cell carcinoma(58;0.151) colorectal|endometrial|ovarian colorectal|endometrial|ovarian D|Mis|N|F|S Lung(47;0.101)|LUSC - Lung squamous cell carcinoma(58;0.151) colorectal|endometrial|ovarian colorectal|endometrial|ovarian D|Mis|N|F|S


Lung(47;0.101)|LUSC - Lung squamous cell carcinoma(58;0.151) colorectal|endometrial|ovarian colorectal|endometrial|ovarian D|Mis|N|F|S Lung(47;0.101)|LUSC - Lung squamous cell carcinoma(58;0.151) colorectal|endometrial|ovarian colorectal|endometrial|ovarian D|Mis|N|F|S meningioma|acoustic meningioma|acoustic neuroma|renal neuroma D|Mis|N|F|S|O meningioma|acoustic meningioma|acoustic neuroma|renal neuroma D|Mis|N|F|S|O meningioma|acoustic meningioma|acoustic neuroma|renal neuroma D|Mis|N|F|S|O meningioma|acoustic meningioma|acoustic neuroma|renal neuroma D|Mis|N|F|S|O meningioma|acoustic meningioma|acoustic neuroma|renal neuroma D|Mis|N|F|S|O Myeloproliferative disorder(178;0.0511) OV - Ovarian serous cystadenocarcinoma(145;5.34e-06)|Epithelial(140;7.77e-06) T|Mis|O TRB@ T-ALL Myeloproliferative disorder(178;0.0511) OV - Ovarian serous cystadenocarcinoma(145;5.34e-06)|Epithelial(140;7.77e-06) T|Mis|O TRB@ T-ALL Myeloproliferative disorder(178;0.0511) OV - Ovarian serous cystadenocarcinoma(145;5.34e-06)|Epithelial(140;7.77e-06) T|Mis|O TRB@ T-ALL GBM - Glioblastoma multiforme(1;4.18e-71)|all Becaplermin(DB00102)|Imatinib(DB00619)|Sunitinib(DB01268) cancers(1;4.76e-45)|LUSC - Lung squamous GIST|idiopathic cell carcinoma(32;0.00256) hypereosinophilic syndrome Mis|O|T FIP1L1 GBM - Glioblastoma multiforme(1;4.18e-71)|all Becaplermin(DB00102)|Imatinib(DB00619)|Sunitinib(DB01268) cancers(1;4.76e-45)|LUSC - Lung squamous GIST|idiopathic cell carcinoma(32;0.00256) hypereosinophilic syndrome Mis|O|T FIP1L1 GBM - Glioblastoma multiforme(1;4.18e-71)|all Becaplermin(DB00102)|Imatinib(DB00619)|Sunitinib(DB01268) cancers(1;4.76e-45)|LUSC - Lung squamous GIST|idiopathic cell carcinoma(32;0.00256) hypereosinophilic syndrome Mis|O|T FIP1L1 KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) R130Q(MDAPCA2B_PROSTATE)|R130Q(MFE296_ENDOMETRIUM)|R130fs*4(AN3CA_EN endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S KIRC - Kidney UCEC renal - Uterine clear cell corpus carcinoma(1;0.214) endometrioid carcinoma (6;0.000228)|all cancers(1;4.16e-84)|GBM glioma| prostate|endometrial harmartoma|glioma| - Glioblastoma prostate|endo multiform 31 D|Mis|N|F|S all_cancers(8;6.9e-71)|all_epithelial(8;4.61e-22)|Acute GBM - Glioblastoma Insulin Glargine multiforme(2;9.98e-18)|LUSC recombinant(DB00047)|Insulin lymphoblastic6leukemia(8;1.1e-21)|all_hematologic(8;2.3e-21)|all_lung(13;1.51e-09)| - Lung squamous Lyspro recombinant(DB00046)|Insulin cell retinoblastoma|sarcoma|breast|small carcinoma(3;0.013) retinoblastoma|sarcoma|breast|sm recombinant(DB00 cell lung D|Mis|N|F|S Ovarian(717;0.0423) medullary thyroid| medullary papillary thyroid| thyroid|pheochrom papillary thyroid Sunitinib(DB01268) 1 T|Mis|N|F H4|PRKAR1A|NCOA4|PCM1|GOLGA5|TRIM33|KTN1|TR Ovarian(717;0.0423) medullary thyroid| medullary papillary thyroid| thyroid|pheochrom papillary thyroid Sunitinib(DB01268) 1 T|Mis|N|F H4|PRKAR1A|NCOA4|PCM1|GOLGA5|TRIM33|KTN1|TR Ovarian(717;0.0423) medullary thyroid| medullary papillary thyroid| thyroid|pheochrom papillary thyroid Sunitinib(DB01268) 1 T|Mis|N|F H4|PRKAR1A|NCOA4|PCM1|GOLGA5|TRIM33|KTN1|TR Ovarian(717;0.0423) medullary thyroid| medullary papillary thyroid| thyroid|pheochrom papillary thyroid Sunitinib(DB01268) 1 T|Mis|N|F H4|PRKAR1A|NCOA4|PCM1|GOLGA5|TRIM33|KTN1|TR Ovarian(717;0.0423) medullary thyroid| medullary papillary thyroid| thyroid|pheochrom papillary thyroid Sunitinib(DB01268) 1 T|Mis|N|F H4|PRKAR1A|NCOA4|PCM1|GOLGA5|TRIM33|KTN1|TR RPL22|MDS1|EVI1|CBFA2T3|CBFA2T1|ETV6|LAF4 T AML|preB- ALL|T-ALL RPL22|MDS1|EVI1|CBFA2T3|CBFA2T1|ETV6|LAF4 T AML|preB- ALL|T-ALL RPL22|MDS1|EVI1|CBFA2T3|CBFA2T1|ETV6|LAF4 T AML|preB- ALL|T-ALL all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ R273H(NCIH1793_LUNG)|R273H(MOLT13_HAEMATOPOIETIC_AND_LYMPHOID_TISSU - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ R175H(KMS26_HAEMATOPOIETIC_AND_LYMPHOID_TISSUE)|R175H(HCC1395_BREAS - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F

all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F all_cancers(10;1.01e-06)|Myeloproliferative GBM - Glioblastoma disorder(207;0.0122)|Prostate(122;0.081) multiforme(2;1.59e-06)|READ - Rectum adenocarcinoma(115;0.174) breast|colorectal|lung|sarcoma|adrenocortical breast|sarcoma|adrenocortical ca 111 Mis|N|F Kidney(1;0.000404)|KIRC - Kidney renal clear1 cell carcinoma(1;0.000569) renal|hemangioma|pheochromocytoma renal|hemangioma|pheochromocy D|Mis|N|F|S Kidney(1;0.000404)|KIRC - Kidney renal clear1 cell carcinoma(1;0.000569) renal|hemangioma|pheochromocytoma renal|hemangioma|pheochromocy D|Mis|N|F|S



CGC_Other_Diseases DNARepairGenes_Role FamilialCancerDatabase_Syndromes MUTSIG_Published_Results 5XA_ref_count_gatk 5XA_alt_count_gatk 5XA_dp_gatk 5XA_t_fraction_gatk 5XA_t_fraction_mutect 0 0 0 0 0.022175 colorectal|pancreatic|desmoid|hepatoblastoma|glioma|other Hereditary_Desmoid_Disease|Familial_Adenomatous_Polyposis|Turcot_syndrome TSP Lung(16;0.13) CNS 0 0 0 0 0.02416 colorectal|pancreatic|desmoid|hepatoblastoma|glioma|other Hereditary_Desmoid_Disease|Familial_Adenomatous_Polyposis|Turcot_syndrome TSP Lung(16;0.13) CNS 0 0 0 0 0.017801 colorectal|pancreatic|desmoid|hepatoblastoma|glioma|other Hereditary_Desmoid_Disease|Familial_Adenomatous_Polyposis|Turcot_syndrome TSP Lung(16;0.13) CNS 0 0 0 0 0 colorectal|pancreatic|desmoid|hepatoblastoma|glioma|other Hereditary_Desmoid_Disease|Familial_Adenomatous_Polyposis|Turcot_syndrome TSP Lung(16;0.13) CNS 0 0 0 0 0 colorectal|pancreatic|desmoid|hepatoblastoma|glioma|other Hereditary_Desmoid_Disease|Familial_Adenomatous_Polyposis|Turcot_syndrome TSP Lung(16;0.13) CNS 0 0 0 0 0.023139 Cardio-facio-cutaneous Cardiofaciocutaneous_syndrome syndrome 0 0 0 0 0.018237 Cardio-facio-cutaneous Cardiofaciocutaneous_syndrome syndrome 0 0 0 0 0 Hereditary_Diffuse_Gastric_Cancer 0 0 0 0 0.025131 Hereditary_Diffuse_Gastric_Cancer 0 0 0 0 0 Hereditary_Diffuse_Gastric_Cancer 0 0 0 0 0 Uveal_Melanoma_Familial|Familial_Malignant_Melanoma_and_Tumors_of_the_Nervous_System|Hered HNSCC(2;