SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01989585

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Phase I/II Study of Dabrafenib, Trametinib, and Navitoclax in BRAF Mutant Melanoma (Phase I and II) and Other Solid Tumors (Phase I Only)

This phase I/II trial studies the side effects and best dose of dabrafenib, trametinib, and navitoclax and to see how well they work in treating patients with BRAF mutant melanoma or solid tumors that have spread to other parts of the body or cannot be removed by surgery. Dabrafenib, trametinib, and navitoclax may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT01989585 BRAF V600E Mutation Present BRAF V600K Mutation Present Metastatic Melanoma Solid Neoplasm Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7
MeSH: Melanoma Skin Neoplasms
HPO: Cutaneous melanoma Melanoma Neoplasm of the skin

5 Interventions

Name: Dabrafenib

Description: Given PO

Type: Drug

Arm I (dabrafenib, trametinib) Arm II (dabrafenib, trametinib, and navitoclax)

Name: Laboratory Biomarker Analysis

Description: Correlative studies

Type: Other

Arm I (dabrafenib, trametinib) Arm II (dabrafenib, trametinib, and navitoclax)

Name: Navitoclax

Description: Given PO

Type: Biological

Arm II (dabrafenib, trametinib, and navitoclax)

Name: Pharmacological Study

Description: Correlative studies

Type: Other

Arm I (dabrafenib, trametinib) Arm II (dabrafenib, trametinib, and navitoclax)

Name: Trametinib

Description: Given PO

Type: Drug

Arm I (dabrafenib, trametinib) Arm II (dabrafenib, trametinib, and navitoclax)


Primary Outcomes

Description: Determined by dose-limiting toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events.

Measure: Recommended phase II dose of the combination of dabrafenib, trametinib, and navitoclax (Phase I)

Time: Up to 28 days

Description: Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, in the cohort of patients treated with dabrafenib, trametinib, and navitoclax (DTN). The proportion of patients with a best response of CR will be presented with a 95% confidence interval calculated using the method of Atkinson and Brown.

Measure: Proportion of patients with a complete response (CR) (Phase II)

Time: Up to 4 weeks after last study treatment

Description: A comparison between the maximal tumor regression for patients treated with DTN and dabrafenib and trametinib (DT) will be conducted using a Wilcoxon rank-sum test.

Measure: Maximal degree of tumor regression (Phase II)

Time: Up to 4 weeks after last study treatment

Secondary Outcomes

Description: PFS will be summarized using the Kaplan-Meier. Log-rank tests will be used to assess for indications of differences between the two treatment modalities.

Measure: Progression free survival (PFS) (Phase II)

Time: Time from start of treatment to time of progression or death, whichever occurs first, assessed for up to 4 years

Description: OS will be summarized using the Kaplan-Meier. Log-rank tests will be used to assess for indications of differences between the two treatment modalities.

Measure: Overall survival (OS) (Phase II)

Time: Up to 4 years

Description: ORRs will be presented with 95% exact, binomial confidence intervals.

Measure: Objective response rate (ORR) (Phase II)

Time: Up to 4 weeks after last study treatment

Other Outcomes

Description: Fold changes of TUNEL will be calculated (post/pre). A Wilcoxon rank-sum test will be used to compare the ratios (or equivalently, the difference in the natural logs) of baseline and follow-up levels of TUNEL between DTN and DT treatment arms.

Measure: Change in terminal deoxynucleotidyl transferase 2´-deoxyuridine, 5´-triphosphate (dUTP) nick end labeling assay (TUNEL) staining

Time: Baseline to up to 1 week

Description: Will be primarily descriptive.

Measure: Change in B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL-2)

Time: Baseline to up to 1 week

Description: Will be primarily descriptive.

Measure: Change in Ki67

Time: Baseline to up to 1 week

Description: Will be primarily descriptive.

Measure: Change in phosphatase and tensin homolog (PTEN) status

Time: Baseline to up to 1 week

Description: Fold-changes in assay response will be calculated (post/pre). Fold changes in the assay will be compared across RECIST responses using the Kruskal-Wallis test. In addition, for assay-based response or progression, the proportions of patients with CR/partial response (PR), stable disease (SD), or progressive disease (PD) will be presented with exact 90% confidence intervals. Assay performance data will be compared with response. The proportions will be summarized and compared using exact confidence intervals. Behavior of the blood assay will be summarized graphically.

Measure: Fold changes in BRAF-mutation assay

Time: Baseline to up to 4 weeks after last study treatment

Description: Assay fold changes will be compared with fold changes in tumor burden (post/pre). The relationship will be summarized graphically and using the Spearman rank correlation. Differences in the behavior of the assay will be explored using a general linear model of log (fold-change) with study, baseline tumor burden, and log (fold-change tumor burden) as predictors.

Measure: Fold changes in tumor burden

Time: Baseline to up to 4 weeks after last study treatment

Description: Descriptive statistics including mean, standard deviation, coefficient of variation, geometric mean, median, minimum and maximum will be computed for each pharmacokinetic variable; descriptive statistics for natural-log transformed pharmacokinetic variables will also be provided.

Measure: Pharmacokinetic parameters, including maximal plasma or serum concentration (Cmax), area under the curve to the last collection point (AUClast), area under the curve for dose interval (AUC0-t), and time of maximal concentration (Tmax)

Time: Pre-treatment, 1, 2, 4, 6, 8, and 24 hours post-treatment on days 1 and 15 of cycle 1, and day 1 of cycles 2, 4, 8, and 12

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There are 2 SNPs

SNPs


1 V600E

Descriptive statistics including mean, standard deviation, coefficient of variation, geometric mean, median, minimum and maximum will be computed for each pharmacokinetic variable; descriptive statistics for natural-log transformed pharmacokinetic variables will also be provided.. Inclusion Criteria: - PHASE I SUBJECTS ONLY: Prior therapy is allowed; for patients enrolled in the Phase I portion of the study, patients may have received any number of prior lines of therapy including treatment with a BRAF and/or MEK inhibitor; prior navitoclax use will not be allowed, unless the patient received < 7 days of navitoclax lead-in on this or another study and had to stop for reasons other than toxicity or disease progression - Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using validated, commercially available assay performed in a Clinical Laboratory Improvement Act [CLIA]-approved laboratory) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective - If test at CLIA-certified lab used a non-Food and Drug Administration (FDA) approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test) - Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam - Prior therapy is allowed; for patients enrolled in the Phase II portion of the study, patients may have received prior immunotherapy (including high-dose IL-2, ipilimumab, nivolumab, and other anti-PD1/PDL1 antibodies) or chemotherapy; however prior navitoclax, BRAF inhibitor and/or MEK inhibitor therapy will not be allowed - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) - Life expectancy of greater than 3 months - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1 x 10^9/L - Hemoglobin >= 9 g/dl (patients may be transfused to this level) - Platelets >= 100,000/mcL - Total bilirubin =< 1.5 x institutional upper limit of normal OR > 1.5 x institutional upper limit of normal allowed if direct bilirubin is within normal range - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal - Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.3 x upper limit of normal (ULN) - Serum creatinine =< 1.5 mg/dL OR creatinine clearance >= 50 mL/min/1.73 --- V600E ---

thyroiditis/hypothyroidism, adrenal insufficiency, hypophysitis) requiring replacement therapy, at the time of randomization - Due to the expected dose-limiting toxicity of thrombocytopenia, the following concomitant medications are not allowed during navitoclax administration: clopidogrel, ibuprofen, tirofiban, warfarin, and other anticoagulants, drugs, or herbal supplements that affect platelet function are excluded, with the exception of low-dose anticoagulation medications (such as heparin) that are used to maintain the patency of a central intravenous catheter; aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor - Current use of a prohibited medication; the following medications or non-drug therapies are prohibited: - Other anti-cancer therapy while on study treatment; (note: megestrol [Megace] if used as an appetite stimulant is allowed) - Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis - Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng) - Anticoagulants or antiplatelet agents except for low-dose, 81 mg aspirin - Preclinical studies indicate that navitoclax is metabolized by CYP3A4, is a moderate inhibitor of CYP2C8, and is a strong inhibitor of CYP2C9; there is also evidence of interactions with dabrafenib; therefore, caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins, and glitazones, whereas CYP2C9 substrates include phenytoin; when possible, investigators should switch to alternative medications or monitor the patients closely; CYP3A inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax or during navitoclax administration - Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible; current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of permeability-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; below are a few examples of the agents: - Strong inducers of CYP3A or CYP2C8: - Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine) - Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, s-mephenytoin - Miscellaneous: bosentan, St. John's wort - Strong inhibitors of CYP3A or CYP2C8 - Antibiotics: clarithromycin, telithromycin, troleandomycin - Antidepressants: nefazodone - Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole - Hyperlipidemia: gemfibrozil - Antiretroviral: ritonavir, saquinavir, atazanavir - Miscellaneous: conivaptan Inclusion Criteria: - PHASE I SUBJECTS ONLY: Prior therapy is allowed; for patients enrolled in the Phase I portion of the study, patients may have received any number of prior lines of therapy including treatment with a BRAF and/or MEK inhibitor; prior navitoclax use will not be allowed, unless the patient received < 7 days of navitoclax lead-in on this or another study and had to stop for reasons other than toxicity or disease progression - Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using validated, commercially available assay performed in a Clinical Laboratory Improvement Act [CLIA]-approved laboratory) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective - If test at CLIA-certified lab used a non-Food and Drug Administration (FDA) approved method, information about the assay must be provided; (FDA approved tests for BRAF V600 mutations in melanoma include: THxID BRAF Detection Kit and Cobas 4800 BRAF V600 Mutation Test) - Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam - Prior therapy is allowed; for patients enrolled in the Phase II portion of the study, patients may have received prior immunotherapy (including high-dose IL-2, ipilimumab, nivolumab, and other anti-PD1/PDL1 antibodies) or chemotherapy; however prior navitoclax, BRAF inhibitor and/or MEK inhibitor therapy will not be allowed - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) - Life expectancy of greater than 3 months - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1 x 10^9/L - Hemoglobin >= 9 g/dl (patients may be transfused to this level) - Platelets >= 100,000/mcL - Total bilirubin =< 1.5 x institutional upper limit of normal OR > 1.5 x institutional upper limit of normal allowed if direct bilirubin is within normal range - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal - Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) < 1.3 x upper limit of normal (ULN) - Serum creatinine =< 1.5 mg/dL OR creatinine clearance >= 50 mL/min/1.73 --- V600E ---

thyroiditis/hypothyroidism, adrenal insufficiency, hypophysitis) requiring replacement therapy, at the time of randomization - Due to the expected dose-limiting toxicity of thrombocytopenia, the following concomitant medications are not allowed during navitoclax administration: clopidogrel, ibuprofen, tirofiban, warfarin, and other anticoagulants, drugs, or herbal supplements that affect platelet function are excluded, with the exception of low-dose anticoagulation medications (such as heparin) that are used to maintain the patency of a central intravenous catheter; aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor - Current use of a prohibited medication; the following medications or non-drug therapies are prohibited: - Other anti-cancer therapy while on study treatment; (note: megestrol [Megace] if used as an appetite stimulant is allowed) - Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis - Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng) - Anticoagulants or antiplatelet agents except for low-dose, 81 mg aspirin - Preclinical studies indicate that navitoclax is metabolized by CYP3A4, is a moderate inhibitor of CYP2C8, and is a strong inhibitor of CYP2C9; there is also evidence of interactions with dabrafenib; therefore, caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins, and glitazones, whereas CYP2C9 substrates include phenytoin; when possible, investigators should switch to alternative medications or monitor the patients closely; CYP3A inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax or during navitoclax administration - Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible; current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of permeability-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; below are a few examples of the agents: - Strong inducers of CYP3A or CYP2C8: - Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine) - Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, s-mephenytoin - Miscellaneous: bosentan, St. John's wort - Strong inhibitors of CYP3A or CYP2C8 - Antibiotics: clarithromycin, telithromycin, troleandomycin - Antidepressants: nefazodone - Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole - Hyperlipidemia: gemfibrozil - Antiretroviral: ritonavir, saquinavir, atazanavir - Miscellaneous: conivaptan BRAF V600E Mutation Present BRAF V600K Mutation Present Metastatic Melanoma Solid Neoplasm Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Melanoma Skin Neoplasms PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of navitoclax when given in combination with dabrafenib and trametinib in patients with BRAF-mutant solid tumors. --- V600E ---


2 V600K

thyroiditis/hypothyroidism, adrenal insufficiency, hypophysitis) requiring replacement therapy, at the time of randomization - Due to the expected dose-limiting toxicity of thrombocytopenia, the following concomitant medications are not allowed during navitoclax administration: clopidogrel, ibuprofen, tirofiban, warfarin, and other anticoagulants, drugs, or herbal supplements that affect platelet function are excluded, with the exception of low-dose anticoagulation medications (such as heparin) that are used to maintain the patency of a central intravenous catheter; aspirin will not be allowed within 7 days prior to the first dose of navitoclax or during navitoclax administration; however, subjects who have previously received aspirin therapy for thrombosis prevention may resume a low dose (i.e., maximum 100 mg QD) of aspirin if platelet counts are stable (>= 50,000/mm^3) through 6 weeks of navitoclax administration; all decisions regarding treatment with aspirin therapy will be determined by the investigator in conjunction with the medical monitor - Current use of a prohibited medication; the following medications or non-drug therapies are prohibited: - Other anti-cancer therapy while on study treatment; (note: megestrol [Megace] if used as an appetite stimulant is allowed) - Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to the first dose of study therapy; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis - Because the composition, pharmacokinetics (PK), and metabolism of many herbal supplements are unknown, the concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], ginkgo biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng) - Anticoagulants or antiplatelet agents except for low-dose, 81 mg aspirin - Preclinical studies indicate that navitoclax is metabolized by CYP3A4, is a moderate inhibitor of CYP2C8, and is a strong inhibitor of CYP2C9; there is also evidence of interactions with dabrafenib; therefore, caution should be exercised when dosing navitoclax concurrently with CYP2C8 and CYP2C9 substrates; common CYP2C8 substrates include paclitaxel, statins, and glitazones, whereas CYP2C9 substrates include phenytoin; when possible, investigators should switch to alternative medications or monitor the patients closely; CYP3A inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax or during navitoclax administration - Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible; current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's wort), or strong inhibitors or inducers of permeability-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; below are a few examples of the agents: - Strong inducers of CYP3A or CYP2C8: - Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine) - Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, s-mephenytoin - Miscellaneous: bosentan, St. John's wort - Strong inhibitors of CYP3A or CYP2C8 - Antibiotics: clarithromycin, telithromycin, troleandomycin - Antidepressants: nefazodone - Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole - Hyperlipidemia: gemfibrozil - Antiretroviral: ritonavir, saquinavir, atazanavir - Miscellaneous: conivaptan BRAF V600E Mutation Present BRAF V600K Mutation Present Metastatic Melanoma Solid Neoplasm Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7 Melanoma Skin Neoplasms PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD), toxicity, and safety profile of navitoclax when given in combination with dabrafenib and trametinib in patients with BRAF-mutant solid tumors. --- V600E --- --- V600K ---



HPO Nodes


HPO:
Cutaneous melanoma
Genes 11
BRAF HRAS XPC CDKN2A POLH ERCC3 BAP1 CXCR4 MC1R NRAS WRN
Melanoma
Genes 64
RAD51 RAD51C TYR RAD51D CDKN2A KRAS CDKN2B RAF1 CDKN2D MRE11 CYSLTR2 ERCC2 KLLN PTPN11 ERCC3 BRIP1 ERCC4 ERCC5 ERCC6 SF3B1 NRAS MGMT BRCA1 MBTPS2 BRAF ACD BRCA2 PIK3CA CXCR4 CTSC POLH POT1 MC1R MITF WRN CHEK2 HRAS BARD1 NBN AKT1 SLC45A2 GNA11 TRPV3 XPA OCA2 XPC GNAQ PTEN MDM2 TERT DDB2 RNF43 PALLD PALB2 TERF2IP SEC23B TP53 SDHB SDHC SDHD SMAD4 BAP1 CDK4 RAD50
Neoplasm of the skin
Genes 171
VEGFC ALX3 CDKN1A PMS1 CDKN1B CYLD CDKN2A KRAS CDKN2B CDKN2C KRT1 KRT5 COL7A1 KRT6B KRT9 TCF3 PMS2 ERCC2 FLT4 KRT14 ERCC3 CIB1 ERCC4 ERCC5 KRT16 CARMIL2 WWOX NRAS KRT17 SASH1 RASA1 PDGFB PDGFRA ING1 PDGFRB DOCK8 PSENEN GJB4 NTHL1 CTSC GJB6 POLH RNF113A TMC6 FERMT1 MC1R WRN BLNK APC IKBKG LAMA3 GPR143 PORCN LAMB3 CASP10 NLRP1 GJC2 LAMC2 RPS20 TSC1 TSC2 XPA MSH2 OCA2 XPC MSH3 OCRL KEAP1 TNFRSF10B DCC PTCH1 WRAP53 PTEN MDM2 FAS FCN3 FASLG TERC ECM1 TERT DDB2 DICER1 STAT1 BAP1 MEN1 FAN1 TNFRSF4 BLM TYR NUTM1 STK4 RMRP TGFBR2 GJA1 MSH6 RASGRP1 BMPR1A GTF2E2 GJB2 GJB3 KLLN MLH3 NF1 GNA14 PMVK MBTPS2 LMNA BRAF RNF6 NF2 TINF2 DCLRE1C SLC17A9 LZTS1 PIK3CA CD28 CXCR4 PIK3R1 FDPS HPGD SLCO2A1 IGHM BRD4 RECQL4 SNAI2 CHEK2 TMC8 HRAS PTCH2 MLH1 MPLKIP PRKAR1A GTF2H5 LRRC8A WNT10A DKC1 FLCN PRKCD SPRED1 CD79A CD79B AKT1 SLC45A2 SMO TRPV3 FGFR1 CTLA4 PLCD1 IGLL1 MMP1 SEMA4A CTNNB1 TNFRSF1B FH KDSR SUFU KIT EPCAM RSPO1 SLX4 SEC23B MUTYH MVD TP53 IL7 MVK NOTCH3 SDHB SDHC SDHD COL1A1