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Gene | ALK |
Variant | T1151dup |
Impact List | duplication |
Protein Effect | unknown |
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, Dec 2023). |
Associated Drug Resistance | Y |
Category Variants Paths |
ALK mutant ALK T1151dup |
Transcript | NM_004304.5 |
gDNA | chr2:g.29222406_29222408 |
cDNA | c.3451_3453 |
Protein | p.T1151 |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.5 | chr2:g.29222406_29222408 | c.3451_3453 | p.T1151 | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29222406_29222408 | c.3451_3453 | p.T1151 | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29222406_29222408 | c.3451_3453 | p.T1151 | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK fusion ALK T1151dup | lung non-small cell carcinoma | no benefit | Ceritinib | Case Reports/Case Series | Actionable | In a clinical case study, Zykadia (ceritinib) treatment did not result in disease control in a patient with non-small cell lung cancer and uterine metastasis harboring an ALK fusion and ALK T1151dup (reported as ALK 1151Tins) whose disease progressed after prior Xalkori (crizotinib) and Alecensa (alectinib) treatments (PMID: 34184417). | 34184417 |
ALK fusion ALK T1151dup | lung non-small cell carcinoma | predicted - sensitive | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in shrinkage of the pulmonary and uterine lesions in a patient with non-small cell lung cancer and uterine metastasis harboring an ALK fusion and ALK T1151dup (reported as ALK 1151Tins), and the patient remained recurrence-free over 1 year of treatment (PMID: 34184417). | 34184417 |
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 |
EML4 - ALK ALK T1151dup | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK T1151dup in culture (PMID: 35421578). | 35421578 |
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 | 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 | 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 | Iruplinalkib | Preclinical - Cell culture | Actionable | In a preclinical study, Iruplinalkib (WX-0593) treatment inhibited viability of transformed cells expressing EML4-ALK with ALK T1151dup in culture (PMID: 35421578). | 35421578 |
ALK rearrange ALK T1151dup ALK G1269A | 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 |