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Gene | ALK |
Variant | S1206Y |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | ALK S1206Y lies within the protein kinase domain of the Alk protein (UniProt.org). S1206Y has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK rearrangements (PMID: 22277784, PMID: 24675041, PMID: 25727400), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Aug 2024). |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK S1206Y |
Transcript | NM_004304.5 |
gDNA | chr2:g.29220734G>T |
cDNA | c.3617C>A |
Protein | p.S1206Y |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.5 | chr2:g.29220734G>T | c.3617C>A | p.S1206Y | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29220734G>T | c.3617C>A | p.S1206Y | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29220734G>T | c.3617C>A | p.S1206Y | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated growth inhibition with Zykadia (ceritinib) treatment in culture (PMID: 24675041). | 24675041 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) inhibited proliferation of transformed cells expressing EML4-ALK with ALK S1206Y in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited Alk phosphorylation and cell proliferation of transformed cells over expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 26144315). | 26144315 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) inhibited viability of a cell line expressing EML4-ALK with ALK S1206Y in culture (PMID: 31446141). | 31446141 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK S1206Y in the context of EML4-ALK in culture (PMID: 27780853). | 27780853 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | conflicting | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to Alunbrig (brigatinib) in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | conflicting | Alectinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK S1206Y in culture and in xenograft models (PMID: 24887559). | 24887559 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | conflicting | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to Alecensa (alectinib) in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | resistant | ASP3026 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated moderate resistance to ASP3026 in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing EML4-ALK with ALK S1206Y demonstrated resistance to Xalkori (crizotinib) in culture (PMID: 25727400). | 25727400 |
EML4 - ALK ALK S1206Y | Advanced Solid Tumor | sensitive | NVL-655 | Preclinical - Cell culture | Actionable | In a preclinical study, NVL-655 inhibited viability of cells expressing EML4-ALK and ALK S1206Y in culture (PMID: 39269178). | 39269178 |
ALK fusion ALK S1206Y | lung non-small cell carcinoma | predicted - resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical study, an ALK S1206Y secondary mutation in the context of an ALK fusion was associated with resistance to Xalkori (crizotinib) in a patient with non-small cell lung cancer (PMID: 22277784). | 22277784 |
ALK rearrange ALK S1206Y | lung non-small cell carcinoma | resistant | Crizotinib | Case Reports/Case Series | Actionable | In a clinical case study, a non-small cell lung cancer patient harboring an ALK rearrangement responded to Xalkori (crizotinib) therapy, but then progressed after 32 months, and was found to have acquired ALK S1206Y (PMID: 25724526). | 25724526 |
ALK rearrange ALK S1206Y | lung non-small cell carcinoma | resistant | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing ALK S1206Y in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784). | 22277784 |