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|Gene Variant Descriptions||ALK T1151dup indicates the insertion of the duplicate amino acid, threonine (T)-1151, in the protein kinase domain of the Alk protein (UniProt.org). T1151dup has been demonstrated to occur as a secondary drug resistance mutation in the context of EML4-ALK (PMID: 22277784, PMID: 20695522), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2020).|
|Associated Drug Resistance||Y|
|Transcript||gDNA||cDNA||Protein||Source Database||Genome Build|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|EML4 - ALK ALK T1151dup||Advanced Solid Tumor||resistant||Crizotinib||Preclinical - Cell culture||Actionable||In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK were resistant to Xalkori (crizotinib) in culture (PMID: 22277784).||22277784|
|EML4 - ALK ALK T1151dup||Advanced Solid Tumor||resistant||Crizotinib||Preclinical - Cell culture||Actionable||In a preclinical study, transformed cells expressing ALK T1151dup in the context of EML4-ALK demonstrated reduced sensitivity to Xalkori (crizotinib) compared to cells expressing EML4-ALK in culture (PMID: 27780853).||27780853|
|EML4 - ALK ALK T1151dup||Advanced Solid Tumor||sensitive||Alectinib||Preclinical - Cell line xenograft||Actionable||In a preclinical study, Alecensa (alectinib) inhibited growth of transformed cells expressing EML4-ALK with ALK T1151dup (referred to as 1151insT) in culture and in xenograft models (PMID: 24887559).||24887559|
|EML4 - ALK ALK T1151dup||Advanced Solid Tumor||sensitive||Brigatinib||Preclinical - Cell culture||Actionable||In a preclinical study, Alunbrig (brigatinib) inhibited growth of transformed cells expressing ALK T1151dup in the context of EML4-ALK in culture (PMID: 27780853).||27780853|
|ALK T1151dup ALK G1269A ALK rearrange||lung non-small cell carcinoma||predicted - resistant||Crizotinib||Case Reports/Case Series||Actionable||In a clinical case study, a non-small cell lung carcinoma patient harboring an ALK rearrangement demonstrated a partial response with Xalkori (crizotinib) treatment, but then progressed after 10.8 months, and was found to harbor secondary resistance mutations, ALK T1151dup and ALK G1269A (PMID: 25724526).||25724526|