Missing content? – Request curation!
Request curation for specific Genes, Variants, or PubMed publications.
Have questions, comments, or suggestions? - Let us know!
Email us at : ckbsupport@genomenon.com
Gene | RET |
Variant | V804M |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | RET V804M lies within the protein kinase domain of the Ret protein (UniProt.org). V804M confers a gain of function on the Ret protein, resulting in increased kinase activity, cell transformation (PMID: 16469774), and is considered a gatekeeper due to lack of response to some inhibitors, including cabozantinib and vandetanib (PMID: 23811235, PMID: 27712045). |
Associated Drug Resistance | Y |
Category Variants Paths |
RET mutant RET act mut RET V804M RET mutant RET V804X RET V804M |
Transcript | NM_020975.6 |
gDNA | chr10:g.43119548G>A |
cDNA | c.2410G>A |
Protein | p.V804M |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_020630.5 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
NM_020975.6 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
NM_001406744.1 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
NM_020975.5 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
NM_001406743.1 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
NM_001406760.1 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
NM_020975 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
NM_020630 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
NM_001406759.1 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
NM_020630.7 | chr10:g.43119548G>A | c.2410G>A | p.V804M | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
RET C634R RET V804M | Advanced Solid Tumor | resistant | Vandetanib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed human cells co-expressing RET C634R and RET V804M were resistant to treatment with Caprelsa (vandetanib) in culture (PMID: 19029224). | 19029224 |
RET V804M RET S904C | medullary thyroid carcinoma | not applicable | N/A | Guideline | Risk Factor | Compound germline RET V804M and S904C mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). | detail... |
RET V804M RET Y806C | medullary thyroid carcinoma | not applicable | N/A | Guideline | Risk Factor | Compound germline RET V804M and Y806C mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). | detail... |
RET V804M RET Y806C | Advanced Solid Tumor | decreased response | Selpercatinib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed human cells expressing RET V804M and Y806C in cis were less sensitive to Retevmo (selpercatinib) in culture (PMID: 35304457). | 35304457 |
RET V804M RET E805K | medullary thyroid carcinoma | not applicable | N/A | Guideline | Risk Factor | Compound germline RET V804M and E805K mutations result in multiple endocrine neoplasia, type 2B (MEN 2B), which is associated with high risk of developing thyroid medullary carcinoma (NCCN.org). | detail... |
RET V804M RET M918T | medullary thyroid carcinoma | resistant | Everolimus + Vandetanib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with thyroid medullary carcinoma harboring RET M918T progressed on multiple therapies, including Nexavar (sorafenib), Caprelsa (vandetanib), Cometriq (cabozantinib), MGCD-516 (sitravatinib), and RXDX-105 (CEP-32496), and upon progression with the combination therapy, Caprelsa (vandetanib) and Afinitor (everolimus), cell-free DNA testing revealed RET M918T and acquisition of a secondary drug resistant mutation, RET V804M (PMID: 29912274; NCT03157128). | 29912274 |
RET V804M RET M918T | medullary thyroid carcinoma | predicted - sensitive | Selpercatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with thyroid medullary cancer harboring RET M918T and RET V804M demonstrated an initial response to Retevmo (selpercatinib), which included a decrease in allelic fraction of RET M918T and RET V804M over 8 weeks and a radiographic response of nearly 54% post 6.9 months of treatment (PMID: 29912274; NCT03157128). | 29912274 |
RET V804M RET M918T | Advanced Solid Tumor | predicted - sensitive | Selpercatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Retevmo (selpercatinib) inhibited cell growth and Ret phosphorylation in transformed cells expressing RET V804M and M918T in culture (PMID: 33161056). | 33161056 |
RET V804M RET G810S RET L881V RET M918T | medullary thyroid carcinoma | predicted - resistant | Selpercatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with hereditary medullary thyroid carcinoma harboring germline RET M918T demonstrated disease progression following an initial response to Retevmo (selpercatinib), and ctDNA sequencing revealed a decrease in RET L881V, but an increase in RET V804M and RET G810S (PMID: 31988000). | 31988000 |
RET V804M RET G810C RET M918T | Advanced Solid Tumor | resistant | Selpercatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing RET V804M, G810C, and M918T were resistant to Retevmo (selpercatinib) treatment in culture (PMID: 33161056). | 33161056 |
RET V804M RET G810S RET M918T | Advanced Solid Tumor | resistant | Selpercatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing RET V804M, G810S, and M918T were resistant to Retevmo (selpercatinib) treatment in culture (PMID: 33161056). | 33161056 |
RET V804M RET Y806C RET M918T | Advanced Solid Tumor | predicted - resistant | Selpercatinib | Preclinical - Biochemical | Actionable | In a preclinical study, transformed human cells expressing RET M918T, V804M, and Y806C in cis were resistant to Retevmo (selpercatinib) in culture (PMID: 35304457). | 35304457 |
RET V804M RET G810S | Advanced Solid Tumor | predicted - sensitive | TY-1091 | Preclinical - Biochemical | Actionable | In a preclinical study, TY-1091 inhibited activity in a cell line expressing RET G810S and V804M in culture (Cancer Res (2023) 83 (7_Supplement): 3419). | detail... |