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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

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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

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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