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Gene | ALK |
Variant | Y1278S |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK Y1278S is a hotspot mutation that lies within the activation loop of the Alk protein (PMID: 24060861, PMID: 25071110). Y1278S results in constitutive activation of Alk and is transforming in cell culture (PMID: 25517749, PMID: 29084134). |
Associated Drug Resistance | |
Category Variants Paths |
ALK mutant ALK act mut ALK Y1278S |
Transcript | NM_004304.5 |
gDNA | chr2:g.29209789T>G |
cDNA | c.3833A>C |
Protein | p.Y1278S |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.5 | chr2:g.29209789T>G | c.3833A>C | p.Y1278S | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29209789T>G | c.3833A>C | p.Y1278S | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29209789T>G | c.3833A>C | p.Y1278S | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK Y1278S | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK Y1278S was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
ALK Y1278S | neuroblastoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a retrospective analysis, Lorbrena (lorlatinib) treatment resulted in a partial response in a neuroblastoma patient harboring ALK Y1278S (PMID: 38787533; NCT04477681). | 38787533 |
ALK Y1278S | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK Y1278S in culture (PMID: 27483357). | 27483357 |
ALK Y1278S | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK Y1278S in culture (PMID: 31852910). | 31852910 |