SNPMiner Trials by Shray Alag


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Report for Mutation R172S

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 2 clinical trials

Clinical Trials


1 A Phase 2 Study of the PARP Inhibitor Olaparib (AZD2281) in IDH1 and IDH2 Mutant Advanced Solid Tumors

This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that have spread to other places in the body (metastatic) and usually cannot be cured or controlled with treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT03212274 Advanced Malignant Solid Neoplasm Glioblastoma Recurrent Cholangiocarcinoma Recurrent Glioma Recurrent Malignant Solid Neoplasm WHO Grade II Glioma WHO Grade III Glioma Drug: Olaparib
MeSH:Glioblastoma Glioma Cholangiocarcinoma Neoplasms
HPO:Cholangiocarcinoma Glioblastoma multiforme Glioma Neoplasm

Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.. Inclusion Criteria: - Subjects must be able to understand the nature of this trial and provide written informed consent, prior to any study specific procedures; patients with Impaired Decision Making Capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) may be considered eligible for this study at the treating physician's discretion, provided that the physician is reasonably sure that the possible risks and benefits of the study are clear and that the patient will take the drug as prescribed - Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins; patients must have IDH1 or IDH2 mutation which must be detected in a clinical accredited laboratory using a Food and Drug Administration (FDA)-approved molecular test or a validated deoxyribonucleic acid (DNA)-based assay conducted in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; only specific mutations that lead to a neomorphic phenotype will be eligible for enrollment, and include IDH1: R132V, R132G, R132S, R132L, R132C and R132H; IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K - Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression); in case of multiple lesions, tumor biopsies will be performed on the most accessible site of disease; all possible precautions to avoid complications will be taken, including discussions in multidisciplinary meetings, if needed; patients affected by glioma will not be considered for study biopsies - Patients must be willing to undergo extra blood sampling for correlative studies - Subjects with extracranial disease must have evaluable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); subjects affected by glioma must have evaluable disease by Response Assessment in Neuro-Oncology Criteria (RANO) criteria - For subjects with glioma, specific inclusion criteria are as follows: - The disease should be recurrent or transformed glioma; subjects must not have had prior surgery (biopsy allowed) or radiation therapy within 3 weeks of enrollment - There must be an enhancing component of disease, as evaluated on pre-treatment magnetic resonance imaging (MRI) - For patients with World Health Organization (WHO) grade III or IV glioma and progressive disease < 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria: - New enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line) - If there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas. --- R132V --- --- R132G --- --- R132S --- --- R132L --- --- R132C --- --- R132H --- --- R140W --- --- R140L --- --- R140Q --- --- R172W --- --- R172G --- --- R172S ---

bosentan, efavirenz, modafinil); the required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents; because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated drug information reference; medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product - Persistent toxicities caused by previous cancer therapy; toxicities should have recovered to =< grade 1, excluding alopecia and stable chronic grade 2 toxicity that is not overlapping with presumed toxicities of olaparib - Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML - Patients with symptomatic uncontrolled brain metastases; a scan to confirm the absence of brain metastases is not required; the patient can receive a stable dose of corticosteroids before and during the study if these were started at least 4 weeks prior to treatment; patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days; patients with known uncontrolled brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events - Major surgery within 2 weeks of starting study treatment; effects from surgeries should have recovered to =< grade 1, with the exception of stable chronic grade 2 that is not overlapping with presumed toxicities of olaparib - Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection; examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent and would limit compliance with study requirements - Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication - Women who are actively breast feeding - Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV); HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Olaparib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated - Patients with a known hypersensitivity to olaparib or any of the excipients of the product; history of allergic reactions attributed to compounds of similar chemica Inclusion Criteria: - Subjects must be able to understand the nature of this trial and provide written informed consent, prior to any study specific procedures; patients with Impaired Decision Making Capacity (IDMC) who have a close caregiver or legally authorized representative (LAR) may be considered eligible for this study at the treating physician's discretion, provided that the physician is reasonably sure that the possible risks and benefits of the study are clear and that the patient will take the drug as prescribed - Subjects must be diagnosed with a glioma, cholangiocarcinoma or other solid malignant tumor that has progressed despite standard therapy, or for which no effective standard therapy exists, with biopsy-confirmed evidence of an IDH1 or IDH2 mutation associated with neomorphic activity of the encoded proteins; patients must have IDH1 or IDH2 mutation which must be detected in a clinical accredited laboratory using a Food and Drug Administration (FDA)-approved molecular test or a validated deoxyribonucleic acid (DNA)-based assay conducted in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; only specific mutations that lead to a neomorphic phenotype will be eligible for enrollment, and include IDH1: R132V, R132G, R132S, R132L, R132C and R132H; IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K - Patients must have tumors determined to be easily accessible for biopsy and must be willing to have serial biopsies (with a third biopsy upon evidence of disease progression); in case of multiple lesions, tumor biopsies will be performed on the most accessible site of disease; all possible precautions to avoid complications will be taken, including discussions in multidisciplinary meetings, if needed; patients affected by glioma will not be considered for study biopsies - Patients must be willing to undergo extra blood sampling for correlative studies - Subjects with extracranial disease must have evaluable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); subjects affected by glioma must have evaluable disease by Response Assessment in Neuro-Oncology Criteria (RANO) criteria - For subjects with glioma, specific inclusion criteria are as follows: - The disease should be recurrent or transformed glioma; subjects must not have had prior surgery (biopsy allowed) or radiation therapy within 3 weeks of enrollment - There must be an enhancing component of disease, as evaluated on pre-treatment magnetic resonance imaging (MRI) - For patients with World Health Organization (WHO) grade III or IV glioma and progressive disease < 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria: - New enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line) - If there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas. --- R132V --- --- R132G --- --- R132S --- --- R132L --- --- R132C --- --- R132H --- --- R140W --- --- R140L --- --- R140Q --- --- R172W --- --- R172G --- --- R172S ---

Primary Outcomes

Description: Will be determined by investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for extracranial solid tumors, Response Assessment in Neuro-Oncology (RANO) criteria for intracranial glioma. Overall response rate and a 90% creditable interval in each cohort will be estimated using the approach described by Koyama. For the other solid tumors cohort, descriptive statistics and graphical displays will be used to summarize results within tumor types.

Measure: Overall response rate

Time: Up to completion of course 8

Secondary Outcomes

Description: For time to event endpoints, Kaplan-Meier curves will be used to demonstrate distributions and median estimates will be reported with 95% confidence intervals. For each cohort, graphical displays such as swimmer plots, will be used to demonstrate patterns of response, progression and death, and in the third cohort they will also indicate disease type.

Measure: Progression-free survival

Time: From start of treatment to time of progression or death, whichever occurs first, assessed up to 1 year

Description: Adverse events will be tabulated by type and grade in each cohort, and also across cohorts.

Measure: Incidence of adverse events

Time: Up to 1 year

Other Outcomes

Description: Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically vs. time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Measure: 2HG plasma magnetic resonance spectroscopy (MRS) levels

Time: Baseline up to post-treatment

Description: Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically vs. time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Measure: 2HG plasma concentration level

Time: Up to 1 year

Description: Will be associated with differential levels of 2HG production, treatment response and resistance. Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically vs. time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Measure: Co-occurring alterations detected via mass cytometry (cyTOF), ribonucleic acid (RNA) sequencing and/or deoxyribonucleic acid (DNA) sequencing

Time: Baseline up to 1 year

2 The PRIME Trial: PARP Inhibition in IDH Mutant Effectiveness Trial. A Phase II Study of Olaparib in Isocitrate Dehydrogenase (IDH) Mutant Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome

This phase II trial studies how well olaparib works in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory), or myelodysplastic syndrome. Patients must also have a change in the gene called the IDH gene (IDH mutation). Olaparib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. This study is being done to see if olaparib is better or worse in treating acute myeloid leukemia or myelodysplastic syndrome compared to the standard chemotherapy drugs.

NCT03953898 Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome IDH1 NP_005887.2:p.R132H IDH2 NP_002159.2:p.R140X Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Therapy-Related Acute Myeloid Leukemia Drug: Olaparib
MeSH:Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Preleukemia Myelodysplastic Syndromes Syndrome
HPO:Acute megakaryocytic leukemia Acute myeloid leukemia Leukemia Myelodysplasia Myeloid leukemia

Only specific mutations that lead to a neomorphic phenotype will be eligible for enrollment, and include those listed below: - IDH1: R132V, R132G, R132S, R132L, R132C and R132H - IDH2: R140W, R140L, R140Q, R172W, R172G, R172S, R172M, R172K. --- R132V --- --- R132G --- --- R132S --- --- R132L --- --- R132C --- --- R132H --- --- R140W --- --- R140L --- --- R140Q --- --- R172W --- --- R172G --- --- R172S ---

Primary Outcomes

Description: The effectiveness of the drug in patients for each cohort will be independently assessed by ORR. The exact two-sided 95% confidence intervals (CI) for the ORR will be reported. The CI based on the Greenwoods variance will be reported.

Measure: Overall response rate (ORR)

Time: Up to 12 months

Description: Will be evaluated by MDS International Working Group (IWG) 2006 criteria (Cheson et al., 2006) and acute myeloid leukemia (AML) IWG 2003 criteria (Cheson et al., 2003) after 6 cycles of treatment. Cumulative ORR will include complete remission (CR), complete remission with incomplete blood count recovery (CRi), partial response (PR), and bone marrow complete remission (marrow CR) achieved at least at one point during these 6 cycles.

Measure: Cumulative ORR

Time: Up to 6 cycles

Secondary Outcomes

Description: Will be estimated using the Kaplan-Meier method with the 95% CIs. The CI based on the Greenwoods variance will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the odds ratios and the adjusted 95% confidence interval will be reported.

Measure: Progression-free survival (PFS)

Time: From first day of therapy to the time of documentation of progression, death of any cause, or last follow-up, whichever comes first, assessed up to 12 months

Description: Will be estimated using the Kaplan-Meier method with the 95% CIs. The CI based on the Greenwoods variance will be reported. In addition, the possible risk factors will be compared for survival with log-rank test. For multivariate analysis, the proportional hazards Cox model will be applied to investigate potential prognostic factors, such as age and stage of disease on the survival data. The adjusted p-values of the odds ratios and the adjusted 95% confidence interval will be reported.

Measure: Overall survival (OS)

Time: From first day of therapy to the time of death or last follow-up, whichever comes first, assessed up to 12 months

Measure: Duration of response (DOR)

Time: From first documentation of response to the time of documentation of progression, death of any cause, or last follow-up, whichever comes first, assessed up to 12 months

Description: Non-hematologic toxicity will be evaluated by Common Terminology Criteria for Adverse Events version 5 criteria.

Measure: Incidence of adverse events

Time: Up to 12 months

Other Outcomes

Description: The Mann-Whitney U test will be used to test for differences in post-treatment plasma 2HG concentrations between patients with a response to treatment and those without. Will also test for differences in Delta2HG (defined as pre-treatment minus post-treatment plasma concentration) between patients with a response to treatment and those without. Differences with p =< 0.05 will be considered significant. The area under the receiver operating characteristic curve (ROC AUC) will be calculated to determine the cutoff value of the Delta2HG difference. The optimal cutoff value will be determined at the point on the ROC curve at (sensitivity + specificity − 1) is maximized.

Measure: Change in 2-hydroxyglutarate (2HG) levels

Time: Up to 12 months

Description: Will define MRD based on the variation of the variant allele frequency of the IDH1/2 mutation in the bone marrow of the patients before and during therapy. Will evaluate two different variables: MRD negativity (defined by the absence of detection of the IDH mutant in the sample) and the molecular response (defined by the log reduction of the frequency of the mutant allele). MRD negativity is a qualitative variable and will be reported as a percentage with 95% confidence interval for each time point and mutation. Will compare the different groups using a Chi-Square test. Molecular response is a quantitative variable reported as a median, min and max for each time point and we will use a student t test for the comparison of the different groups.

Measure: Minimal residual disease (MRD) assessment

Time: Up to 12 months

Description: Will be estimated using Poisson distribution model as the fraction of positive reads divided by total reads containing a target. The limit of detection will be defined for each mutation as the mean value of IDH1/2 wild-type controls plus three standard deviations.

Measure: Mutant allele frequency

Time: Up to 12 months


HPO Nodes


HP:0002664: Neoplasm
Genes 1515
EPCAM BAP1 CYLD WT1 CTBP1 GLI3 CTNNB1 ELMO2 ATRX TERT EDN3 MTAP TSC2 RAD51 BLNK KCNAB2 WDPCP SPINK1 ARID1B PTEN STK11 XPA PTH1R TCF4 EPCAM NF1 GPC3 ERCC3 MC1R CASP10 PDGFRA RPL5 CDH1 BRIP1 RUNX1 KRAS SFTPC GPR35 MYLK STS DYNC2LI1 RAG2 CBL FOXE1 STAT3 TTC37 ABL1 NSD1 ATM KCNH1 GPR101 IGH KRT17 SUFU TERT KRAS GPC3 CYP11B2 MLH3 PTCH1 FAH MSH2 EXT1 CCND1 MSH3 ATP7A SEC23A PHOX2B HAX1 MYD88 LMO1 PIK3CA PRLR AXIN1 TCF4 RUNX1 AKT1 ERBB2 REST DCLRE1C SERPINA1 ERCC3 TMC6 RASA1 MSH3 TRNL1 CALR HRAS INS RNF113A SETBP1 CDH1 SLC37A4 TFAP2A CDH1 PTCH1 KIT PTEN IL1RN MLH3 MUTYH PTEN KIT GBA BCL2 KCNH1 GINS1 ESCO2 TET2 SLX4 DICER1 PALB2 NEK1 ESCO2 COL7A1 PTCH2 WT1 WRN GCM2 BRD4 BRAF TREX1 THPO SUFU NRAS CDC73 POU6F2 GNAS DAXX BUB3 RSPO1 MNX1 ERCC2 RPS28 ANTXR2 CTNNB1 POT1 FANCA KDM6B RET MST1 NOTCH3 FGFR1 KRAS LYST CHIC2 TMC6 MET KRT10 UROD SLC25A11 ARSA EVC2 TEK XRCC2 CASP8 ASCL1 IL1B TERF2IP DICER1 MPL OFD1 RHBDF2 DICER1 MDM2 WT1 MMP1 CDKN2A FGF8 NR4A3 FGFR2 OCRL TP53 ERCC2 SUFU ERCC4 ALX4 TINF2 DCLRE1C SRY SRP72 NF2 GNAS LETM1 TP53 FANCB TAL1 TDGF1 BRCA1 LEMD3 NF2 BRAF NUP214 RAD21 COL18A1 SDHD ICOS CEP57 BAP1 FANCM PTPRJ FANCE SLC22A18 PIK3R1 JAK2 FLT4 SMO WIPF1 DLST NF2 RAD50 MEN1 CHEK2 GPC4 WDPCP CYP2A6 HBB GANAB XRCC4 TET2 ATP7B EP300 DIS3L2 HFE CARD14 OFD1 ALX3 VANGL1 BAP1 SDHB EXTL3 PIK3CA GATA2 ALX3 BCL10 KIT WAS FGFR2 RMRP TWIST1 BMPR1B DIS3L2 ERCC3 FOXP1 SMAD4 CALR APC PCGF2 USP8 DMPK NRAS DKC1 BRCA1 ADAR BCR RSPO1 SLC45A2 GJC2 TNFRSF4 AKT1 IFIH1 MSH6 DICER1 PAX6 TGFBR2 SRY KLHDC8B CPLX1 MSH6 AIP PMS1 CREBBP ERCC2 CTSA APC MMP1 SH2B3 PKD1 TRNF SEC23B DNAJC21 STK11 BCR HBB MITF IGLL1 ALX4 MDH2 AKT1 SCN4A SDHAF2 PRKN PLA2G2A RNF43 DNMT3A TERT NSD2 RMRP FANCG BRCA2 CAT TP53 BMPR1A MAD2L2 SIX6 DDB2 GREM1 KRT17 PAX4 RPS17 TRPV3 ERCC4 C11ORF95 APC IL12RB1 BRIP1 PPM1D SDHB NODAL HNF1A FLT4 MSH6 ERCC6 BTK SLC26A4 SEMA3C AR NEK1 TERC RPL35A RPS20 CDKN1C SF3B1 TERC PTEN RFWD3 BRCA2 KCNQ1OT1 RPL10 ACTG2 MAGT1 ALK BLM H19 LEMD3 RPL31 MLLT10 PYGL RPL15 IRF1 CR2 MITF PTEN MYC PTPN11 TUBB TCF4 KCNQ1 NFKB2 ALX1 HLA-DRB1 APC EWSR1 NBN CDKN2A ERCC4 GCK DLL1 SLC25A11 PDGFB L2HGDH PRKCD CTC1 PIK3CA SUFU RPL27 KIF1B SRC CIB1 RECQL4 CDKN2B MSH3 BRCA2 PALB2 PDE6D SDHC SDHD CCL2 CHEK2 PMVK XPC STK11 PIK3CA MVD DHCR7 KIT GPC6 KARS1 MNX1 VHL TUBB NAB2 KEAP1 TSC1 NQO2 APC SDHB VHL TCTN3 RECQL4 PMS2 RAD51C STAG3 SNAI2 MAP3K8 SETBP1 SDHB NPM1 RAD51C RARA ERBB2 ERCC5 ATRX CHEK2 KRAS BRCA1 TFAP2A SLCO2A1 PHOX2B PTEN COL2A1 PIGL PDGFRA APC CPLANE1 AURKA SDHD LAMA3 VHL RPS26 GFI1B CDKN1B PRDM16 AXIN2 FZD2 AP2S1 LZTR1 TP53 TP53 GNA14 CTNNB1 MSTO1 PIK3CA RPS29 CALR DHX37 MYF6 SDHC MALT1 ELANE SDHD SLC26A4 MAP3K1 GDNF MSH2 SDHC TGFBR1 RUNX1 CREB1 CDKN2A TSC2 KRAS TNFRSF10B LMNA WWOX PHOX2B EDN3 RPS10 RSPRY1 TRIM37 RET MEN1 BCL10 MSH2 TNFRSF13C FOXE1 FANCC H19-ICR BLM ERCC6 LIG4 BDNF LMOD1 NF2 TMEM107 CYLD GJB2 EXT1 CTSC PHOX2B RAD51D RASGRP1 RB1 TGFBR2 SRY MYH8 KRAS TINF2 RECQL4 H19 PRF1 GDNF MXI1 SMPD1 WT1 HRAS COL1A1 PDGFRB FAS FANCD2 NF1 DISP1 PDGFRL IKBKG BIN1 BRCA2 ADA POLE AXIN2 SEMA4A KRAS NRAS PALB2 CHEK2 ASCL1 POLE TLR2 PIK3CA MINPP1 SOS1 CYLD CTLA4 POT1 ASXL1 CDC73 APC SAMD9L WT1 TRAF7 GATA4 PIK3CA DYNC2LI1 ATP7A CBFB MST1R GCGR MPL COL4A5 SMAD4 CDKN1A SDHD TRIM28 POLH GPR101 PIK3CA FLCN GPR143 RB1 SBDS SLC12A3 KLF6 ICOS GNB1 PIGA TYROBP GFI1 RAD51 SLC26A2 MC1R TREM2 SFTPA2 JAG1 BAP1 EGFR IGH KIT PLCB4 NLRP1 HNF1B ZFHX3 EPHB2 KLLN OCA2 WT1 FAH FH TERT SRD5A3 LIG4 NFKB1 RNF43 KIT STAT1 IFNG BMPR1A ERCC3 TBX18 TET2 MAP2K1 EXT2 HRAS RTEL1 FGFR3 PTEN CTNNB1 MAP2K2 MEN1 APC CLCNKB AKT1 ESCO2 CDC73 MS4A1 BRAF CRKL NUTM1 CDK4 NTHL1 ETV6 TET2 SQSTM1 FAM20C PIGL SEC23A ATM PALB2 TYR SRSF2 EXT2 GJB2 DNMT3A HRAS TCOF1 CHEK2 CDH1 FH DKC1 POLE PIK3CA PTCH2 AKT1 PAX3 FH ADAMTS3 APC PMS1 RAD51C PLCD1 PUF60 DIS3L2 CDH23 SCN9A FOXC2 SMARCB1 CDKN2A VANGL2 ENG SH2D1A SDHB SOX9 BRAF SDHA PGM3 ERCC2 GJB2 TBC1D24 CHD7 MPL DHH PTCH1 CALR IL12A TNFRSF13B CD28 MLH1 PTPN12 OFD1 MLH3 REST CCDC22 APPL1 COL14A1 IGH PSENEN IL2RG MC1R SMARCA4 CYLD KIF11 PHKG2 JAK2 COL2A1 AXIN2 FLNA WNT5A TYR EP300 GLI3 EXT2 MGAT2 KCNE3 ECE1 PARN IDH2 TSC1 ARL6IP6 FGFR3 SMAD4 HMBS SLC6A17 PRKAR1A BAP1 KDSR DHCR24 CXCR4 DDX41 GABRD RET NR0B1 DMRT3 CCND1 GDF5 POU6F2 CTLA4 TBXT FANCA NRTN PHKA2 KIT ITK RNASEH2A PERP CDC73 OFD1 CYP2D6 RET MEN1 CD27 PARN FUZ RPS19 MSH2 SMARCE1 TNFSF12 ZSWIM6 TERT RHOH NF1 BUB1B SLX4 LIG4 PDGFRL TNFSF15 OPCML APC PRKCD SETD2 RPS19 BRCA1 FAT4 ANTXR1 WNT10A SUFU TP63 EFL1 IL7 MN1 DOCK8 CDC73 SSX1 TMEM231 MPLKIP VHL MINPP1 BIRC3 PDX1 STS PSAP HNF1A JAK2 FANCL POT1 GNAS TERT CD79A KLF11 WRN MAPRE2 LIG4 CYSLTR2 DNM2 SH3GL1 KIT FOXH1 RELA KRAS PRKAR1A ERBB3 FGFR2 H19 TJP2 CD81 PNP MSH6 WT1 THPO ATP6V1B2 GNAQ BRCA1 WRAP53 ERCC3 CHRNG KRT14 TSC1 DLC1 CTNNB1 FGFRL1 SDHC GDNF HABP2 NRAS ATR TRNK BMPR1A TERT BRAF AKT1 XPC FGFR3 NUP214 TRIP13 SMARCD2 ZSWIM6 PIEZO2 EVC IL6 HRAS GPC4 TNFRSF13B PALLD CDKN2A POLR1D TP53 FOXO1 BRCA2 FIBP CDH23 RB1CC1 B3GALT6 FLT3 GJA1 SH2B3 MRAP MTOR AR FOXI1 TP53 GNAQ KRT6B MYD88 KRT16 TP53 NF1 MYSM1 MGMT KIT NF1 GPC4 GCM2 SIX3 PIK3CA RAD21 HRAS PMS2 ASCC1 BRCA2 GAS1 FASLG SDHD NRAS C2CD3 KDR SDHA SMAD4 SOX2 NBEAL2 SRGAP1 AGGF1 ATM AKT1 RPGRIP1L NOD2 BAX BRCA2 H19-ICR TGIF1 MAPK1 ESR1 EXT1 RPL11 KRAS BCL10 SKI LAMB3 XIAP SDHC HABP2 TRNS1 CCM2 FIBP PIK3CA TRIM28 HRAS SCN10A NF1 WT1 CPLANE1 HFE F5 C2CD3 GNPTAB TBX2 KLF6 GATA2 VEGFC RNASEH2B CBL SEMA3D ARMC5 CXCR4 JAK2 IGF2 FGFR2 NRAS UBE2T ARHGAP26 SCN11A MEN1 LMX1B F13A1 BCR COMP EDN1 SDHC ACTB GDNF CDKN2C ASPSCR1 NAGS PDGFRB PALB2 DLEC1 BCL10 STAR GNA11 PORCN RNR1 FLCN SPIB WT1 RET SDHB SLC22A18 ERCC4 CDKN2A CTHRC1 DLST OGG1 POLD1 DCC IL2RG REST SRP54 RAF1 TSC1 SRP54 IDH1 ACD KIT ACAN NSD2 TOP2A CASP10 DVL1 PTPN11 CASP10 STIM1 KRT9 AR CIB1 GNAS AR VAMP7 MRE11 GFI1 RPS14 BCL10 CACNA1S TP53 VANGL1 SKIV2L PTCH2 G6PC LRP5 PDGFRB BARD1 RPS27 RPS7 GNAS ENPP1 STAT6 ACVR1 MTM1 NEUROD1 TNFRSF13C PKD2 RUNX1 STK11 FGF3 TRIP13 SIX1 BRCA2 LAMC2 NELFA DVL3 GJB4 NSUN2 CDKN1B CTNNB1 POLR1C GJB3 SMARCB1 SBDS LMNA KRAS TRNH ECM1 STK4 ANTXR2 SOS1 BAP1 MSX2 DICER1 SDHB ACD WRAP53 BRCA1 ATP7A BUB1B RYR1 RET BRCA2 TP53 DPM1 BRCA2 BCR POLD1 TCIRG1 PTPN11 HOXD13 CR2 TARS1 JAK2 BMP2 MUTYH FLT3 TRNS2 MTMR14 NR5A1 ABCA5 RET AHCY TSC2 KIT KCNQ1OT1 RNF6 RAD54L HNF1A HMMR RNF139 WWOX TCTN3 BRAF FCN3 RNASEH2C AIP PRKN SF3B1 MSH6 NSD1 PTCH2 CCBE1 RECQL4 PMS2 ERCC2 HNF4A MMEL1 BUB1 TET2 TRPS1 ABCC6 RET IRF5 CDKN2B PDGFB USP9X TAL2 INTU GNAS HDAC4 MFN2 DYNC2H1 PIK3CA PLAG1 ATM MAX FAS PIK3CA CYP11B1 CCND1 H19-ICR PTCH1 MUTYH ABL1 ODC1 FGFR2 COL7A1 MSR1 BRCA1 RB1 TNFRSF1B COL7A1 FLT4 GPC3 TGFBR2 ATRX RAG1 PRCC BRAF TNFRSF1B FANCE RAD54L CBL SDHB TERT SDHD RPS24 FASLG MET KRT17 GATA1 ERBB2 FGFR1 KAT6B ABCA5 SDHAF2 SLC25A13 NOP10 GATA2 RFWD3 PDGFRA SPRTN MLH1 NKX2-1 IGF2R CD19 MAP3K1 TREX1 TRNP ZFPM2 CTNNB1 TRNQ WWOX IGHM MYH11 TMEM127 CDON NF2 SAMD9 PTEN RNASEL IDH2 HNF4A GTF2H5 GLI3 HRAS LPP DDB2 KIT PIK3CA PDCD10 HSPG2 HFE RPL26 BRIP1 ASXL1 SDHD CEBPA ACVRL1 NRAS CD19 GNAQ TET2 TCTN3 SMARCB1 FLCN ABCB11 BLK RAD54B SDHC FH AKT1 ANTXR1 FANCF HNF1B EXOC6B SAMHD1 SHOX MYO1H COL11A2 KCNJ10 TRIP13 CC2D2A LZTS1 SEC23B GPR101 DOCK8 BRCA2 NBN SLC26A2 SPRED1 VHL KRT1 LIN28B GTF2E2 NRAS ZIC2 SNAI2 SH3KBP1 SHOX BCL6 NTHL1 RHBDF2 CD28 MCM4 CCND1 FANCG SMARCAD1 GATA2 RERE YY1 ASXL1 IL7R TMEM67 C1S TAF1 FGFR3 NBN KRAS KIF1B AIP KCNJ11 LETM1 FANCI MLH1 MBTPS2 NRAS NEK9 GNAI3 APC2 EYA1 ZAP70 EXT2 BUB1 SSX2 LIG4 CARMIL2 SLC17A9 TMC8 PCNA EPAS1 TFE3 BRCA2 DHH MAP2K1 CASP8 CDK4 PDGFB RTEL1 EWSR1 PTEN VHL GJB6 NDP RNF6 TNPO3 TGFBR2 TXNRD2 PNP TAF15 TRNK SMO NOTCH1 LRRC8A RASA1 TSC2 ABCC8 PRKAR1A BAX IDH1 SLC22A18 ADA FAN1 TG PTEN BMPR1A MSTO1 ERCC5 IRF1 MLH1 NRAS MLH1 PICALM FANCD2 SF3B1 BICC1 RPS15A TERT KLLN ELANE FAM149B1 GATA1 SASH1 INPP5E TP53 WT1 BMPR1A PTPN11 PTPN11 MYCN XPA EDNRB TP53 FLI1 GDF2 PHB BMPER FGFR3 PTEN MCC EXT1 MC2R KCNN3 DNASE1L3 DHCR7 RASGRP1 SHH NPM1 SLC26A2 SLC37A4 IGF2 RPL18 SH2B3 PTCH1 BRAF PAX7 INHBA BMPR1A KIF7 XRCC3 IGF2 POU2AF1 DNAJC21 CYP26C1 RB1 MPL REST KIAA0753 DNMT3A ERCC6 MUC5B MLH3 ASXL1 MPL NOTCH3 KCNJ10 SMARCE1 TSR2 RPL10 KRT1 SLC25A13 WT1 NNT TP53 GNA11 GLI1 BARD1 FLCN COL7A1 SRP54 GLI2 EDN3 PTPN3 WT1 TMEM127 CD79B GATA2 TERC FN1 EIF2AK4 RAD51 WASHC5 SAMD9L AIP TP53 AAGAB RB1 TP53 KRT5 ADA2 HSPA9 PIK3CA SRSF2 PHF21A IDH1 KRAS KRAS CHEK2 BUB1B RET FANCC TP53 WHCR RAD54B NUMA1 SDHB HMBS TMEM216 SMAD4 MAFA MSH2 RPL35 CDKN1B IGF2 PPP2R1B CD70 CEL MAD1L1 MAX ALK GPC3 FERMT1 KIF1B TCF3 POLH PIK3R1 USF3 FDPS MYC DNAJC21 TNFSF12 HACE1 CDH1 SDHA ND5 NHP2 PIK3CA RPS14 NBN WNT10A ING1 CASR SUFU FGFR3 HPGD BTK ENG DCC CASP8 PHOX2B STAC3 USB1 KRIT1 PHOX2B TET2 SMAD4 JAK2 BCHE APC MVK SMAD7 SMO DKC1 SMARCB1 VHL F13B TINF2 USP8 FGFR1 FOXI1 TET2 CD96 TET2 JAK2 KRAS