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Gene | ALK |
Variant | R1192P |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | ALK R1192P lies within the protein kinase domain of the Alk protein (UniProt.org). R1192P confers a gain of function to the Alk protein as demonstrated by increased downstream signalling (PMID: 21838707), activation in in vitro assays (PMID: 33674381, PMID: 25517749), and transformation of cultured cells (PMID: 21838707, PMID: 33674381, PMID: 25517749). |
Associated Drug Resistance | |
Category Variants Paths |
ALK mutant ALK act mut ALK R1192P |
Transcript | NM_004304.5 |
gDNA | chr2:g.29220776C>G |
cDNA | c.3575G>C |
Protein | p.R1192P |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_004304.5 | chr2:g.29220776C>G | c.3575G>C | p.R1192P | RefSeq | GRCh38/hg38 |
NM_004304 | chr2:g.29220776C>G | c.3575G>C | p.R1192P | RefSeq | GRCh38/hg38 |
NM_004304.4 | chr2:g.29220776C>G | c.3575G>C | p.R1192P | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ALK R1192P | malignant pheochromocytoma | predicted - sensitive | Brigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Alunbrig (brigatinib) treatment resulted in a partial response (PR) after 2 months of therapy and a sustained PR at 10 months in a patient with malignant pheochromocytoma harboring ALK R1192P (PMID: 34371380). | 34371380 |
ALK R1192P | Advanced Solid Tumor | sensitive | Brigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a transformed cell line expressing ALK R1192P was sensitive to Alunbrig (brigatinib) in culture, resulting in cell growth inhibition (PMID: 27049722). | 27049722 |
ALK R1192P | Advanced Solid Tumor | sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) treatment inhibited Alk phosphorylation and viability in transformed cells expressing ALK R1192P in culture (PMID: 27483357). | 27483357 |
ALK R1192P | Advanced Solid Tumor | sensitive | Repotrectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Augtyro (repotrectinib) decreased Alk phosphorylation and neurite outgrowth in cells expressing ALK R1192P in culture (PMID: 31852910). | 31852910 |
ALK R1192P | malignant pheochromocytoma | no benefit | Alectinib + Octreotide | Case Reports/Case Series | Actionable | In a clinical case study, addition of Alecensa (alectinib) to Octreotide treatment did not lead to a response in a patient with malignant pheochromocytoma harboring ALK R1192P, with a radiological stable disease after 1 month of treatment and disease progression after 5 months of treatment (PMID: 34371380). | 34371380 |