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Report for Clinical Trial NCT01947023

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 1 Study of Dabrafenib in Combination With Lapatinib in BRAF Mutant Thyroid Cancer

This phase I trial studies the side effects and best dose of lapatinib when given together with dabrafenib in treating patients with thyroid cancer that cannot be removed by surgery and has not responded to previous treatment (refractory). Dabrafenib and lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT01947023 Metastatic Thyroid Gland Carcinoma Unresectable Thyroid Gland Carcinoma
MeSH: Carcinoma Thyroid Neoplasms Thyroid Diseases
HPO: Abnormality of the thyroid gland Carcinoma Neoplasm of the thyroid gland Thyroid adenoma Thyroid carcinoma Thyroid follicular adenoma

4 Interventions

Name: Dabrafenib

Description: Given PO

Type: Drug

Treatment (lapatinib, dabrafenib)

Name: Dabrafenib Mesylate

Description: Given PO

Type: Drug

Treatment (lapatinib, dabrafenib)

Name: Lapatinib

Description: Given PO

Type: Drug

Treatment (lapatinib, dabrafenib)

Name: Lapatinib Ditosylate

Description: Given PO

Type: Drug

Treatment (lapatinib, dabrafenib)


Primary Outcomes

Description: Will be defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity MTD is defined as the highest dose at which not more than 1/6 of the patients experience dose limiting toxicity.

Measure: Maximum tolerated dose (MTD) of lapatinib, in combination with the established dose of dabrafenib

Time: First 42 days of treatment

Secondary Outcomes

Description: Tissues such as phosphorylated mitogen-activated protein kinase 1 (ERK), human epidermal growth factor receptor (HER) 2, HER3, epidermal growth factor receptor (EGFR), platelet derived growth factor (PDGF), or protein kinase B (AKT) will be examined. Mean percent change will be calculated and compared.

Measure: Mean percent change in the post-treatment tissues relative to pre-treatment tissues for the phosphorylated protein targets examined

Time: Baseline to day 7 of cycle 1

Description: Genes including sodium/iodide symporter (NIS), dual-specificity phosphatase 5 (DUSP5), and plasminogen activator (PLAT) will be examined. Mean percentage change is calculated and compared with respect to each genotype.

Measure: Mean percentage change in transcript levels in the post-treatment tissues relative to pre-treatment tissues for several genes analyzed by reverse-transcriptase-polymerase chain reaction

Time: Baseline to day 7 of cycle 1

Purpose: Treatment

Single Group Assignment


There are 2 SNPs

SNPs


1 V600E

Mean percentage change is calculated and compared with respect to each genotype.. Inclusion Criteria: - Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective - Patients must have measurable and histologically or cytologically confirmed thyroid cancer with a BRAF V600E or V600K (c. --- V600E ---

1799 T to A and c.1799_1800TG>AA) mutation that is not considered curable by surgery; confirmation will be done at Memorial Sloan Kettering (MSK); only tumors with a BRAFV600E or BRAFV600K mutation will be eligible for the clinical study; BRAF status will be assessed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; BRAF status may also be tested with any Food and Drug Administration (FDA)-approved test (such as Cobas 4800 BRAF V600 Mutation Test) - The tumor is considered to be radioactive-iodine refractory by any of the following criteria: - Total lifetime dose of radioactive iodine > 600 mCi - Absent or insufficient radioactive iodine uptake in either all lesions or an index lesion which has never been resected or received external beam radiation therapy as documented on a radioactive iodine scan (insufficient uptake must be confirmed by either an endocrinologist or nuclear medicine physician) - Progression of disease (by imaging or thyroglobulin) within 6 months of radioactive iodine treatment - Fludeoxyglucose F 18 (FDG)-avid lesion (standard uptake variable maximum [SUVmax] >= 3) on a FDG-positron emission tomography (PET) scan - No recent treatment for thyroid cancer as defined as: - No radioactive iodine therapy is allowed if given < 3 months prior to initiation of this protocol therapy; a diagnostic study using < 10 mCi of radioactive iodine (RAI) is not considered radioactive iodine therapy - No external beam radiation therapy < 4 weeks prior to initiation of therapy on this protocol - No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed < 4 weeks prior to the initiation of therapy - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or Karnofsky >= 60% - Life expectancy of greater than 2 months - Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels - Absolute neutrophil count (ANC) >= 1.2 x 10^9/L, within 2 weeks of the first dose of study treatment - Hemoglobin >= 9 g/dL, within 2 weeks of the first dose of study treatment - Platelets >= 100 x 10^9/L, within 2 weeks of the first dose of study treatment - Bilirubin =< 1.5 x institutional upper limit of normal (ULN) except subjects with known Gilbert's syndrome, within 2 weeks of the first dose of study treatment - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN, within 2 weeks of the first dose of study treatment - Blood creatinine =< 1.5 mg/dL (if blood creatinine is > 1.5 mg/dL, calculate creatinine clearance using standard Cockcroft and Gault method or using a 24 hour urine collection for creatinine; creatinine clearance must be > 50 mL/min), within 2 weeks of the first dose of study treatment - Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with PT/INR/PTT established within the therapeutic range prior to randomization; subjects will be eligible if it is determined by a hematologist that the cause is not associated with clinical bleeding (e.g., deficiency of factor XII), within 2 weeks of the first dose of study treatment - Left ventricular ejection fraction >= institutional lower limit of normal (LLN) by echocardiogram (ECHO), within 2 weeks of the first dose of study treatment - Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of study treatment - The effects of dabrafenib on the developing human fetus are unknown; for this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (barrier method of birth control, or abstinence; hormonal contraception is not allowed due to drug-drug interactions which can render hormonal contraceptives ineffective) for the duration of study participation, and for at least 2 weeks after treatment with dabrafenib; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately - Ability to understand and the willingness to sign a written informed consent document - Patient must agree to allow 3 separate biopsies of any malignant lesion; biopsies do not need to be done if: - Tumor is not considered accessible by either the investigator or the person performing the biopsy (it is determined the risk is too high due to location near vital organs or too great of a risk of an adverse event) - Patient is on anticoagulation and it would be unsafe to temporarily hold the anticoagulation - Consent of the principal investigator (PI) not to have a biopsy done - A minimum of 8 subjects must participate in the biopsy part of the study Exclusion Criteria: - Prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment - Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study treatment and during the study - Current use of a prohibited medication; patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A (CYP3A) or cytochrome P450, family 2, subfamily C, polypeptide 8 (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 P-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; it is important to regularly consult a frequently-updated list of these agents; 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 - Prohibited: strong inducers of CYP3A or CYP2C8, since concentrations of dabrafenib may be decreased - Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine) - Anticonvulsant: carbamazepine, oxcarbazepine phenobarbital, phenytoin, s-mephenytoin - Miscellaneous: bosentan, St. John's wort - Prohibited: strong inhibitors of CYP3A or CYP2C8, since concentrations of dabrafenib may be increased - Antibiotics: clarithromycin, telithromycin, troleandomycin - Antidepressant: nefazodone - Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole - Hyperlipidemia: gemfibrozil - Antiretroviral: ritonavir, saquinavir, atazanavir - Miscellaneous: conivaptan - Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) grade 2 or higher from previous anti-cancer therapy, except alopecia; in specific cases, will be allowed with permission from the principal investigator - Human immunodeficiency virus (HIV)-positive patients on antiviral drugs and/or cluster of differentiation (CD)4 count is inadequate (< 500); if neither condition exists, HIV-positive patients are eligible - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - A history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (with the exception of cleared HBV and HCV infection, which will be allowed) - Presence of an invasive malignancy other than the study indication under this trial within 3 years of study enrollment except for carcinoma in situ CIS, squamous cell carcinomas of the skin, or basal cell carcinoma of the skin; a diagnosis of an invasive malignancy within 3 years is allowed if both the cure rate is felt to be > 80% and there has been no evidence of disease in the past year - Patients with a history of RAS mutation-positive tumors are not eligible regardless of interval from the current study; Note: prospective RAS testing is not required; however if the results of previous RAS testing are known, they must be used in assessing eligibility - Brain metastases that are symptomatic or requiring corticosteroids (except inhaled); subjects must also be off of enzyme-inducing anticonvulsants for > 4 weeks - History or evidence of cardiovascular risks including any of the following: - History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization - History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system - Intra-cardiac defibrillators - Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study - History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible - Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy - Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO) - Medical or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with dabrafenib, breastfeeding should be discontinued if the mother is treated with dabrafenib; these potential risks may also apply to other agents used in this study Inclusion Criteria: - Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective - Patients must have measurable and histologically or cytologically confirmed thyroid cancer with a BRAF V600E or V600K (c. --- V600E ---


2 V600K

Mean percentage change is calculated and compared with respect to each genotype.. Inclusion Criteria: - Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective - Patients must have measurable and histologically or cytologically confirmed thyroid cancer with a BRAF V600E or V600K (c. --- V600E --- --- V600K ---

1799 T to A and c.1799_1800TG>AA) mutation that is not considered curable by surgery; confirmation will be done at Memorial Sloan Kettering (MSK); only tumors with a BRAFV600E or BRAFV600K mutation will be eligible for the clinical study; BRAF status will be assessed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; BRAF status may also be tested with any Food and Drug Administration (FDA)-approved test (such as Cobas 4800 BRAF V600 Mutation Test) - The tumor is considered to be radioactive-iodine refractory by any of the following criteria: - Total lifetime dose of radioactive iodine > 600 mCi - Absent or insufficient radioactive iodine uptake in either all lesions or an index lesion which has never been resected or received external beam radiation therapy as documented on a radioactive iodine scan (insufficient uptake must be confirmed by either an endocrinologist or nuclear medicine physician) - Progression of disease (by imaging or thyroglobulin) within 6 months of radioactive iodine treatment - Fludeoxyglucose F 18 (FDG)-avid lesion (standard uptake variable maximum [SUVmax] >= 3) on a FDG-positron emission tomography (PET) scan - No recent treatment for thyroid cancer as defined as: - No radioactive iodine therapy is allowed if given < 3 months prior to initiation of this protocol therapy; a diagnostic study using < 10 mCi of radioactive iodine (RAI) is not considered radioactive iodine therapy - No external beam radiation therapy < 4 weeks prior to initiation of therapy on this protocol - No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed < 4 weeks prior to the initiation of therapy - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 or Karnofsky >= 60% - Life expectancy of greater than 2 months - Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels - Absolute neutrophil count (ANC) >= 1.2 x 10^9/L, within 2 weeks of the first dose of study treatment - Hemoglobin >= 9 g/dL, within 2 weeks of the first dose of study treatment - Platelets >= 100 x 10^9/L, within 2 weeks of the first dose of study treatment - Bilirubin =< 1.5 x institutional upper limit of normal (ULN) except subjects with known Gilbert's syndrome, within 2 weeks of the first dose of study treatment - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional ULN, within 2 weeks of the first dose of study treatment - Blood creatinine =< 1.5 mg/dL (if blood creatinine is > 1.5 mg/dL, calculate creatinine clearance using standard Cockcroft and Gault method or using a 24 hour urine collection for creatinine; creatinine clearance must be > 50 mL/min), within 2 weeks of the first dose of study treatment - Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.3 x institutional ULN; subjects receiving anticoagulation treatment may be allowed to participate with PT/INR/PTT established within the therapeutic range prior to randomization; subjects will be eligible if it is determined by a hematologist that the cause is not associated with clinical bleeding (e.g., deficiency of factor XII), within 2 weeks of the first dose of study treatment - Left ventricular ejection fraction >= institutional lower limit of normal (LLN) by echocardiogram (ECHO), within 2 weeks of the first dose of study treatment - Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of study treatment - The effects of dabrafenib on the developing human fetus are unknown; for this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (barrier method of birth control, or abstinence; hormonal contraception is not allowed due to drug-drug interactions which can render hormonal contraceptives ineffective) for the duration of study participation, and for at least 2 weeks after treatment with dabrafenib; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately - Ability to understand and the willingness to sign a written informed consent document - Patient must agree to allow 3 separate biopsies of any malignant lesion; biopsies do not need to be done if: - Tumor is not considered accessible by either the investigator or the person performing the biopsy (it is determined the risk is too high due to location near vital organs or too great of a risk of an adverse event) - Patient is on anticoagulation and it would be unsafe to temporarily hold the anticoagulation - Consent of the principal investigator (PI) not to have a biopsy done - A minimum of 8 subjects must participate in the biopsy part of the study Exclusion Criteria: - Prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment - Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study treatment and during the study - Current use of a prohibited medication; patients receiving any medications or substances that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A (CYP3A) or cytochrome P450, family 2, subfamily C, polypeptide 8 (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 P-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; it is important to regularly consult a frequently-updated list of these agents; 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 - Prohibited: strong inducers of CYP3A or CYP2C8, since concentrations of dabrafenib may be decreased - Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine) - Anticonvulsant: carbamazepine, oxcarbazepine phenobarbital, phenytoin, s-mephenytoin - Miscellaneous: bosentan, St. John's wort - Prohibited: strong inhibitors of CYP3A or CYP2C8, since concentrations of dabrafenib may be increased - Antibiotics: clarithromycin, telithromycin, troleandomycin - Antidepressant: nefazodone - Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole - Hyperlipidemia: gemfibrozil - Antiretroviral: ritonavir, saquinavir, atazanavir - Miscellaneous: conivaptan - Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) grade 2 or higher from previous anti-cancer therapy, except alopecia; in specific cases, will be allowed with permission from the principal investigator - Human immunodeficiency virus (HIV)-positive patients on antiviral drugs and/or cluster of differentiation (CD)4 count is inadequate (< 500); if neither condition exists, HIV-positive patients are eligible - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - A history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (with the exception of cleared HBV and HCV infection, which will be allowed) - Presence of an invasive malignancy other than the study indication under this trial within 3 years of study enrollment except for carcinoma in situ CIS, squamous cell carcinomas of the skin, or basal cell carcinoma of the skin; a diagnosis of an invasive malignancy within 3 years is allowed if both the cure rate is felt to be > 80% and there has been no evidence of disease in the past year - Patients with a history of RAS mutation-positive tumors are not eligible regardless of interval from the current study; Note: prospective RAS testing is not required; however if the results of previous RAS testing are known, they must be used in assessing eligibility - Brain metastases that are symptomatic or requiring corticosteroids (except inhaled); subjects must also be off of enzyme-inducing anticonvulsants for > 4 weeks - History or evidence of cardiovascular risks including any of the following: - History of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within the past 24 weeks prior to randomization - History or evidence of current class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system - Intra-cardiac defibrillators - Abnormal cardiac valve morphology (>= grade 2) documented by ECHO; (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study); subjects with moderate valvular thickening should not be entered on study - History or evidence of current clinically significant uncontrolled cardiac arrhythmias; clarification: subjects with atrial fibrillation controlled for > 30 days prior to dosing are eligible - Treatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy - Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO) - Medical or psychiatric illness/social situations that would limit compliance with study requirements - Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with dabrafenib, breastfeeding should be discontinued if the mother is treated with dabrafenib; these potential risks may also apply to other agents used in this study Inclusion Criteria: - Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective - Patients must have measurable and histologically or cytologically confirmed thyroid cancer with a BRAF V600E or V600K (c. --- V600E --- --- V600K ---



HPO Nodes


HPO:
Abnormality of the thyroid gland
Genes 465
UBR1 PTEN CLPB TBC1D24 BIRC3 HNF1B TMEM67 BCOR OPA1 RAI1 TRNL1 MMP2 NNT LHX4 SLC16A2 POU2AF1 IQSEC2 TGIF1 GREM1 TREX1 CDON POU1F1 WDR11 DICER1 SALL1 PROKR2 RASGRP1 PAX8 DNAH1 NSDHL XRCC4 SDHD PRKCD LRP4 PTRH2 LEPR RET IYD PCSK1 KEAP1 DICER1 FOXI1 POLG PMM2 FGF8 MARS1 ENPP1 CDKN2C GPC1 TSHR DISP1 TSHR GLI3 FOXE1 FOXA2 TBX1 NKX2-1 EYA1 ALG8 HIRA CEP57 MLXIPL HSD17B3 CDH23 LEP CLIP2 TRNF MSTO1 LHX3 BUB1B FLCN PDE4D SEMA3C LIG4 PAX8 GLI2 TRAPPC9 MEN1 IFIH1 SRGAP1 CTLA4 DUOX2 KISS1R KCNJ18 PTEN TBL2 ALMS1 ROBO1 AIP MINPP1 DCAF17 BMPR1A FANCI SPIB PIK3C2A ARVCF MC2R MST1 SEC24C TG IL2RG SUFU HESX1 GNAS THRB KCNJ10 JMJD1C IL12RB1 MEN1 TRNS1 ND5 MMEL1 SEMA3D COMT TSHR TSHR SUFU LIFR SKI STAT3 APC TRNL2 TTC37 INSR GTF2I TDGF1 NRTN TXNRD2 TWNK FOXP1 TBX2 SMARCB1 TRNH PMS2 IDH1 PROP1 PRDM16 IYD LHX4 GNAS NNT TSHR PAX8 DLL1 SLC26A4 TRNL1 NKX2-1 GNAS SLC5A5 LRBA POLG TSHR GABRD GP1BB SIX3 POLR3A POU1F1 SKIV2L VPS13A KRAS NODAL GNAS XRCC4 MSH2 GATA6 IGSF1 CHD7 SEMA3E EDNRB TTC7A NRAS DDOST SLC26A4 DUOXA2 TRNS1 CACNA1S TSHB RAI1 CDKN1A RPS20 KCNJ18 SRD5A3 FOXP3 FBLN5 TRH TPO HPD GPR161 KAT6B FGFR1 COX1 THRB SAA1 STAR MRAP EDN3 NKX2-5 SCN4A FOXE1 CDC73 TG TRNW COX3 EFEMP2 RREB1 FOXE1 TSHR LHX4 NKX2-5 IL12A RNASEH2A DICER1 TGFBR2 NKX2-5 COX2 PAX8 MINPP1 FAS APC LIG4 DUOX2 POLR1D USP9X GLI3 RRM2B FMR1 PLAA C1S SASH1 BTNL2 SEC23B NLRP1 HRAS NKX2-1 NIN GABRA3 ADA TCOF1 FASLG ZFAT CDC73 CLCNKB PROP1 THRB RMRP APC SLC5A5 PRKAR1A FOXI1 RCBTB1 BCL10 BAZ1B APC LIG4 OTX2 WFS1 POU3F4 GAS1 HSD17B3 ND4 RFC2 RERE DACT1 MSH3 PIK3CA MMP14 THRA SLC26A4 ALX4 IDH2 FAN1 TWNK TRNQ TBX1 MSH3 GTF2IRD1 RAI1 CDKN2B PROP1 HESX1 TRNN C1QBP ARNT2 RET CDON CCBE1 CDH23 TNFSF15 RBM28 BRAF IFNG SOX3 SUGCT ITCH BMP4 PRKAR1A GPR35 STAT1 CTNS CASP10 CACNA1C LHX3 TRIP13 B3GLCT JAG1 KIAA0556 DEAF1 KDM6A TSC1 CTNNB1 PTEN FUCA1 ELN GLIS3 PLVAP FLCN KMT2D PTCH1 SIX1 BUB3 TSC1 RET LEPR PLCG2 SLC25A4 FUT8 EXOSC2 DNM1L PDGFB WFS1 POU1F1 ELN SRY MLH3 ND6 DUOXA2 SETBP1 STEAP3 FOXH1 TG DMXL2 HNF4A KAT6B UFD1 FMR1 EIF2AK3 PMS1 TNPO3 ECE1 CACNA1S TSC2 APOE AKT1 SGPL1 WDR4 RAG1 SDHC MLH1 MCM8 LMNA TF POLG2 EXT2 TSC2 NF2 BUB1 PIEZO1 FOXP3 PPP1R15B MSH6 RET APC HABP2 KCNJ10 FOXD3 LHX4 GLI2 CASR ZIC2 TRNW ARL6IP6 DCLRE1C FAS HESX1 TRNS2 IL7R STUB1 PRKAR1A POLR1C NPHS1 PIK3CA POMC ALMS1 FOXE1 LIMK1 TSHB RNASEH2B GNE STAT1 GDNF AIRE APC PDE4D SHH AKT1 TPO IL2RA HLA-DRB1 PROP1 FDX2 TRHR ACP5 SOX3 SLC12A3 HABP2 CDC73 DNAJC19 ND1 CDKN1B CHD7 IGH ADAR SLC26A4 MEN1 FOXE1 RNASEH2C TANGO2 EPCAM NKX2-1 TCF4 KLLN ADAMTSL1 SEC23B SEMA4A ZBTB20 PIK3CA GCH1 FLII RAG2 BMPR1A HBB USP9X ABCC6 SALL1 CTNS WRN PTEN MALT1 PTEN SDHB KCNAB2 MSTO1 DUOX2 CEP57 IRF5 CP TBX1 CDKN1B TSHR GATA1 TONSL SAMHD1 PHF21A ATRX DCLRE1C
Carcinoma
Genes 16
POLE MSH2 DKC1 SMARCA4 NLRP1 POLD1 CDKN1B MLH1 RSPO1 FGFR3 BCL10 APC STK11 PTEN APC KIT
Neoplasm of the thyroid gland
Genes 91
ECE1 CASP10 NRTN PTEN JAG1 AKT1 SDHC PTEN MLH1 HABP2 PMS2 APC CDC73 EDN3 LMNA FLCN CDKN1B SEMA3C CDC73 TG GREM1 SLC26A4 DICER1 MSH3 MSH6 RET GNAS APC HABP2 PIK3CA RASGRP1 KCNJ10 EPCAM RET KLLN SRGAP1 SDHD PRKCD SEC23B PTEN TGFBR2 SEMA4A PIK3CA FAN1 MINPP1 FAS RET MINPP1 APC MSH3 BMPR1A FAS KRAS CDKN2B KEAP1 DICER1 MSH2 FOXI1 BMPR1A EDNRB PRKAR1A NRAS MLH3 SEC23B WRN PTEN HRAS PTEN SLC26A4 CDKN2C RET PIK3CA NKX2-1 FOXE1 SDHB KCNJ10 FASLG MEN1 CDKN1A RPS20 CDC73 SEMA3D PRKAR1A FOXE1 CDKN1B GDNF PMS1 APC AKT1 APC FOXI1
Thyroid adenoma
Genes 19
CDKN1B FAS CASP10 CDC73 MSH3 FAS FASLG CDKN2B MEN1 CDKN1A AKT1 MSH3 PIK3CA RASGRP1 PRKAR1A PTEN CDKN1B PRKCD CDKN2C
Thyroid carcinoma
Genes 53
CASP10 JAG1 SDHC HABP2 APC CDC73 FLCN TG GREM1 SLC26A4 DICER1 APC HABP2 RASGRP1 KCNJ10 RET KLLN SRGAP1 SDHD PRKCD SEC23B PTEN PIK3CA MINPP1 FAS RET MINPP1 APC FAS KEAP1 DICER1 FOXI1 BMPR1A PRKAR1A NRAS SEC23B WRN PTEN HRAS SLC26A4 RET NKX2-1 FOXE1 SDHB KCNJ10 FASLG CDC73 PRKAR1A FOXE1 APC AKT1 APC FOXI1
Thyroid follicular adenoma