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Gene | ALK |
Variant | T1151M |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | ALK T1151M lies within the protein kinase domain and inhibitor binding region of the Alk protein (UniProt.org). T1151M has been demonstrated to occur as a secondary drug resistance mutation in the context of ALK fusions (PMID: 28676215, PMID: 27009859), is not transforming in culture but is activating in in vitro assays (PMID: 33674381, PMID: 25517749), and therefore, is predicted to lead to a gain of Alk protein function. |
Associated Drug Resistance | Y |
Transcript | NM_004304.4 |
gDNA | chr2:g.29222407G>A |
cDNA | c.3452C>T |
Protein | p.T1151M |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.4 | chr2:g.29222407G>A | c.3452C>T | p.T1151M | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29222407G>A | c.3452C>T | p.T1151M | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK T1151M | Advanced Solid Tumor | predicted - sensitive | TPX-0131 | Preclinical - Biochemical | Actionable | In a preclinical study, TPX-0131 inhibited kinase activity of ALK T1151M in an in vitro assay (PMID: 34158340). | 34158340 |
EML4 - ALK ALK T1151M | Advanced Solid Tumor | sensitive | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK T1151M | Advanced Solid Tumor | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK T1151M | Advanced Solid Tumor | sensitive | AZD3463 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD3463 inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK T1151M | Advanced Solid Tumor | resistant | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to Zykadia (ceritinib) in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK T1151M | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alunbrig (brigatinib) inhibited the growth of transformed cells expressing EML4-ALK with ALK T1151M in culture (PMID: 27009859). | 27009859 |
EML4 - ALK ALK T1151M | Advanced Solid Tumor | resistant | ASP3026 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cell lines harboring EML4-ALK with ALK T1151M were resistant to ASP3026 in culture (PMID: 27009859). | 27009859 |
ALK rearrange ALK T1151M ALK G1202R | lung non-small cell carcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, a patient with ALK-rearranged non-small cell lung cancer progressed on treatment with Lorbrena (lorlatinib) and subsequent testing of the tumor biopsy revealed ALK G1202R and ALK F1174L whereas testing of single isolated circulating tumor cells (CTC) revealed ALK G1202R and ALK F1174C in one CTC sample and ALK G1202R and ALK T1151M in the second CTC sample (PMID: 31439588). | 31439588 |
EML4 - ALK ALK T1151M ALK C1156Y ALK F1174L ALK G1202R ALK S1206F ALK G1269A | lung adenocarcinoma | predicted - resistant | Lorlatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lorbrena (lorlatinib) treatment resulted in disease progression after 3.7 months therapy in a patient with lung adenocarcinoma harboring EML4-ALK and ALK G1202R, at disease progression, ALK F1174L in cis wth ALK G1202R was identified in biopsies, and ALK C1156Y, G1269A, S1206F, and T1151M were identified in ctDNA (PMID: 31585938). | 31585938 |
Molecular Profile | Protein Effect | Treatment Approaches |
---|---|---|
ALK T1151M | gain of function - predicted | ALK Inhibitor |
EML4 - ALK ALK T1151M | Alectinib AZD3463 Brigatinib Crizotinib | |
ALK rearrange ALK T1151M ALK G1202R | ||
EML4 - ALK ALK T1151M ALK C1156Y ALK F1174L ALK G1202R ALK S1206F ALK G1269A |