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Gene | RET |
Variant | D898_E901del |
Impact List | deletion |
Protein Effect | gain of function |
Gene Variant Descriptions | RET D898_E901del results in the deletion of four amino acids in the protein kinase domain of the Ret protein from amino acids 898 to 901 (UniProt.org). D898_E901del confers a gain of function to Ret as demonstrated by increased Erk phosphorylation (PMID: 32284345), increased Ret phosphorlyation, (PMID: 37535881), cytokine-independent growth in culture (PMID: 32284345, PMID: 37535881), and tumor formation in a mouse model (PMID: 37535881). |
Associated Drug Resistance | |
Category Variants Paths |
RET mutant RET act mut RET D898_E901del |
Transcript | NM_020975.6 |
gDNA | chr10:g.43120167_43120178del12 |
cDNA | c.2694_2705del12 |
Protein | p.D898_E901delDVYE |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001406760.1 | chr10:g.43120167_43120178del12 | c.2694_2705del12 | p.D898_E901delDVYE | RefSeq | GRCh38/hg38 |
NM_001406771.1 | chr10:g.43126665_43126676del12 | c.2692_2703del12 | p.N898_P901delNNAP | RefSeq | GRCh38/hg38 |
NM_020975.6 | chr10:g.43120167_43120178del12 | c.2694_2705del12 | p.D898_E901delDVYE | RefSeq | GRCh38/hg38 |
NM_001406764.1 | chr10:g.43123690_43123701del12 | c.2692_2703del12 | p.L898_I901delLWEI | RefSeq | GRCh38/hg38 |
NM_001406770.1 | chr10:g.43124923_43124934del12 | c.2692_2703del12 | p.K898_V901delKRPV | RefSeq | GRCh38/hg38 |
NM_001406743.1 | chr10:g.43120167_43120178del12 | c.2694_2705del12 | p.D898_E901delDVYE | RefSeq | GRCh38/hg38 |
NM_001406773.1 | chr10:g.43126665_43126676del12 | c.2692_2703del12 | p.N898_P901delNNAP | RefSeq | GRCh38/hg38 |
NM_020630.7 | chr10:g.43120167_43120178del12 | c.2694_2705del12 | p.D898_E901delDVYE | RefSeq | GRCh38/hg38 |
NM_001406759.1 | chr10:g.43120167_43120178del12 | c.2694_2705del12 | p.D898_E901delDVYE | RefSeq | GRCh38/hg38 |
NM_001406769.1 | chr10:g.43126623_43126634del12 | c.2692_2703del12 | p.D898_L901delDDGL | RefSeq | GRCh38/hg38 |
NM_001406762.1 | chr10:g.43123690_43123701del12 | c.2692_2703del12 | p.L898_I901delLWEI | RefSeq | GRCh38/hg38 |
NM_020630.5 | chr10:g.43120167_43120178del12 | c.2694_2705del12 | p.D898_E901del | RefSeq | GRCh38/hg38 |
NM_001406744.1 | chr10:g.43120167_43120178del12 | c.2694_2705del12 | p.D898_E901delDVYE | RefSeq | GRCh38/hg38 |
NM_001406763.1 | chr10:g.43123696_43123707del12 | c.2692_2703del12 | p.E898_T901delEIVT | RefSeq | GRCh38/hg38 |
NM_001406768.1 | chr10:g.43124901_43124912del12 | c.2694_2705del12 | p.C899_Q902delCWKQ | RefSeq | GRCh38/hg38 |
NM_001406767.1 | chr10:g.43124923_43124934del12 | c.2692_2703del12 | p.K898_V901delKRPV | RefSeq | GRCh38/hg38 |
NM_001406772.1 | chr10:g.43126623_43126634del12 | c.2692_2703del12 | p.D898_L901delDDGL | RefSeq | GRCh38/hg38 |
NM_001406766.1 | chr10:g.43124923_43124934del12 | c.2692_2703del12 | p.K898_V901delKRPV | RefSeq | GRCh38/hg38 |
NM_020975.5 | chr10:g.43120167_43120178del12 | c.2694_2705del12 | p.D898_E901del | RefSeq | GRCh38/hg38 |
NM_001406761.1 | chr10:g.43123690_43123701del12 | c.2692_2703del12 | p.L898_I901delLWEI | RefSeq | GRCh38/hg38 |
NM_001406765.1 | chr10:g.43123696_43123707del12 | c.2692_2703del12 | p.E898_T901delEIVT | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
RET D898_E901del | Advanced Solid Tumor | sensitive | Selpercatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Retevmo (selpercatinib) inhibited Erk phosphorylation and growth of transformed cells expressing RET D898_E901del in culture (PMID: 32284345). | 32284345 |
RET D898_E901del | Advanced Solid Tumor | sensitive | Selpercatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Retevmo (selpercatinib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET D898_E901del in culture (PMID: 37535881). | 37535881 |
RET D898_E901del | Advanced Solid Tumor | sensitive | Pralsetinib | Preclinical - Cell culture | Actionable | In a preclinical study, Gavreto (pralsetinib) inhibited Erk phosphorylation and growth of transformed cells expressing RET D898_E901del in culture (PMID: 32284345). | 32284345 |
RET D898_E901del | medullary thyroid carcinoma | predicted - resistant | Vandetanib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del demonstrated primary resistance to Caprelsa (vandetanib) treatment (PMID: 37535881). | 37535881 |
RET D898_E901del | medullary thyroid carcinoma | predicted - sensitive | Selpercatinib | Case Reports/Case Series | Actionable | In a clinical case study, Retevmo (selpercatinib) treatment resulted in a 61% reduction in the sum of the diameters of the target lesions in a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del, with treatment lasting 1 year (PMID: 37535881). | 37535881 |
RET D898_E901del | medullary thyroid carcinoma | predicted - sensitive | Selpercatinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (LIBRETTO-001), Retevmo (selpercatinib) treatment resulted in a clinical response after one month, with a partial response in liver lesions and abdominal lymph nodes that was maintained for 24 months, in a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del (PMID: 38438731; NCT03157128). | 38438731 |
RET D898_E901del | Advanced Solid Tumor | resistant | Cabozantinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing RET D898_E901del were resistant to Cometriq (Cabometyx, cabozantinib) in culture (PMID: 37535881). | 37535881 |
RET D898_E901del | Advanced Solid Tumor | predicted - sensitive | Vandetanib | Preclinical - Cell culture | Actionable | In a preclinical study, Caprelsa (vandetanib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET D898_E901del, but to a lesser degree than cells expressing RET C634R in culture (PMID: 37535881). | 37535881 |