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| Gene | ALK |
| Variant | D1091N |
| Impact List | missense |
| Protein Effect | unknown |
| Gene Variant Descriptions | ALK D1091N lies within the cytoplasmic domain of the Alk protein (UniProt.org). D1091N results in increased ERK activation in the presence of agonist antibodies (PMID: 23104988), but does not transform cultured cells (PMID: 23104988), and therefore, its effect on Alk protein function is unknown. |
| Associated Drug Resistance | |
| Category Variants Paths |
ALK mutant ALK D1091N |
| Transcript | NM_004304.5 |
| gDNA | chr2:g.29223430C>T |
| cDNA | c.3271G>A |
| Protein | p.D1091N |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_004304 | chr2:g.29223430C>T | c.3271G>A | p.D1091N | RefSeq | GRCh38/hg38 |
| NM_004304.4 | chr2:g.29223430C>T | c.3271G>A | p.D1091N | RefSeq | GRCh38/hg38 |
| NM_004304.5 | chr2:g.29223430C>T | c.3271G>A | p.D1091N | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ALK D1091N | neuroblastoma | predicted - sensitive | Alectinib | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) treatment in a neuroblastoma cell line harboring ALK D1091N resulted in decreased cell viability, inhibition of colony formation, and inhibition of Pi3k pathway signaling in culture (PMID: 28455243). | 28455243 |
| ALK D1091N | neuroblastoma | predicted - sensitive | Alectinib + Doxorubicin | Preclinical - Cell culture | Actionable | In a preclinical study, Alecensa (alectinib) treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243). | 28455243 |
| ALK D1091N | neuroblastoma | sensitive | AZD3463 | Preclinical - Cell culture | Actionable | In a preclinical study, AZD3463 treatment in a neuroblastoma cell line harboring ALK D1091N resulted in inhibition of colony formation, repression of Pi3k signaling, and induction of apoptosis in culture (PMID: 26786851). | 26786851 |
| ALK D1091N | neuroblastoma | sensitive | AZD3463 + Doxorubicin | Preclinical - Cell culture | Actionable | In a preclinical study, AZD3463 treatment enhanced the cytotoxic effects of Adriamycin (doxorubicin) in a neuroblastoma cell line harboring ALK D1091N, demonstrating increased apoptotic activity and decreased cell viability in culture (PMID: 28455243). | 28455243 |
| ALK D1091N | neuroblastoma | sensitive | Ceritinib | Preclinical - Cell culture | Actionable | In a preclinical study, Zykadia (ceritinib) decreased viability of a neuroblastoma cell line harboring ALK D1091N in culture (PMID: 38032104). | 38032104 |
| ALK D1091N | neuroblastoma | sensitive | Crizotinib | Preclinical - Cell culture | Actionable | In a preclinical study, Xalkori (crizotinib) decreased viability of a neuroblastoma cell line harboring ALK D1091N in culture (PMID: 38032104). | 38032104 |
| ALK D1091N | neuroblastoma | predicted - sensitive | Lorlatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lorbrena (lorlatinib) decreased viability of a neuroblastoma cell line harboring ALK D1091N in culture (PMID: 38032104). | 38032104 |