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Gene | FGFR2 |
Variant | N550K |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR2 N550K (corresponds to N549K in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). N550K results in increased Fgfr2 kinase activity (PMID: 32723837, PMID: 23908597) and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR2 mutant FGFR2 act mut FGFR2 N550K |
Transcript | NM_022970.4 |
gDNA | chr10:g.121498520A>C |
cDNA | c.1650T>G |
Protein | p.N550K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001144914.1 | chr10:g.121487991A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121498520A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121498520A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_022970.3 | chr10:g.121498520A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_022970.4 | chr10:g.121498520A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_001144913 | chr10:g.121498520A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_001144914 | chr10:g.121487991A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_001144914.1 | chr10:g.121487991A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_001144919.2 | chr10:g.121488063A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_001144919 | chr10:g.121488063A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_001144919.1 | chr10:g.121488063A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
NM_022970 | chr10:g.121498520A>C | c.1650T>G | p.N550K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 N550K | estrogen-receptor positive breast cancer | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 N550K in culture (PMID: 32723837). | 32723837 |
FGFR2 N550K | endometrial cancer | predicted - sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, AZD4547 treatment induced cell death in an endometrial cancer cell line harboring FGFR2 N550K in culture (PMID: 30537101). | 30537101 |
FGFR2 N550K | endometrial cancer | predicted - sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, endometrial cells harboring Fgfr2 N550K were less sensitive to the anti-proliferative effects of AZD4547 than the Fgfr2 double mutant, K310R, N550K (PMID: 26294741). | 26294741 |
FGFR2 N550K | estrogen-receptor positive breast cancer | sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, AZD4547 treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 N550K in culture (PMID: 32723837). | 32723837 |
FGFR2 N550K | endometrial cancer | predicted - sensitive | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) treatment induced cell death in an endometrial cancer cell line harboring FGFR2 N550K in culture (PMID: 30537101). | 30537101 |
FGFR2 N550K | Advanced Solid Tumor | resistant | Dovitinib | Preclinical | Actionable | In a preclinical study, transformed cells expressing FGFR2 N550K were resistant to treatment with Dovitinib (TKI258) (PMID: 23908597). | 23908597 |
FGFR2 N550K | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited Fgfr2 phosphorylation and proliferation in transformed cells expressing FGFR2 N550K (PMID: 23908597). | 23908597 |
FGFR2 N550K | endometrial cancer | predicted - sensitive | PD173074 | Preclinical - Cell culture | Actionable | In a preclinical study, PD173074 treatment induced cell death in an endometrial cancer cell line harboring FGFR2 N550K in culture (PMID: 30537101). | 30537101 |
FGFR2 N550K | Advanced Solid Tumor | resistant | PD173074 | Preclinical | Actionable | In a preclinical study, transformed cells expressing FGFR2 N550K were resistant to PD173074 (PMID: 23908597). | 23908597 |
FGFR2 N550K | Advanced Solid Tumor | sensitive | PRN1371 | Preclinical - Cell culture | Actionable | In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing FGFR2 N550K in culture (PMID: 28978721). | 28978721 |
FGFR2 N550K | estrogen-receptor positive breast cancer | sensitive | SHP099 | Preclinical - Cell culture | Actionable | In a preclinical study, SHP099 treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 N550K in culture (PMID: 32723837). | 32723837 |
FGFR2 N550K | estrogen-receptor positive breast cancer | sensitive | FIIN-2 | Preclinical - Cell culture | Actionable | In a preclinical study, FIIN-2 treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 N550K in culture (PMID: 32723837). | 32723837 |
FGFR2 N550K | endometrial cancer | sensitive | ABT-737 + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, an endometrial cancer cell line harboring FGFR2 N550K demonstrated increased cell death following treatment with Truseltiq (infigratinib) and ABT-737 combination compared to either agent alone in culture (PMID: 30537101). | 30537101 |
FGFR2 N550K | endometrial cancer | sensitive | ABT-737 + Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, an endometrial cancer cell line harboring FGFR2 N550K demonstrated increased cell death following treatment with AZD4547 and ABT-737 combination compared to either agent alone in culture (PMID: 30537101). | 30537101 |
FGFR2 N550K | endometrial cancer | sensitive | ABT-737 + PD173074 | Preclinical - Cell culture | Actionable | In a preclinical study, an endometrial cancer cell line harboring FGFR2 N550K demonstrated increased cell death following treatment with PD173074 and ABT-737 combination compared to either agent alone in culture (PMID: 30537101). | 30537101 |
FGFR2 N550K | estrogen-receptor positive breast cancer | sensitive | FIIN-3 | Preclinical - Cell culture | Actionable | In a preclinical study, FIIN-3 treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 N550K in culture (PMID: 32723837). | 32723837 |
FGFR2 N550K | endometrial cancer | predicted - sensitive | TYRA-200 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TYRA-200 demonstrated activity in an endometrial cancer cell line harboring FGFR2 N550K in culture and treatment resulted in 80% tumor regression in a cell line xenograft model (Eur J Cancer 2022 Vol 174, Supp 1:S16). | detail... |
FGFR2 N550K | Advanced Solid Tumor | predicted - sensitive | TYRA-200 | Preclinical - Cell culture | Actionable | In a preclinical study, TYRA-200 inhibited FGFR2 N550K in an in vitro assay and demonstrated activity in cells expressing FGFR2 N550K in culture (Eur J Cancer 2022 Vol 174, Supp 1:S16). | detail... |