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Gene | FGFR2 |
Variant | W290C |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR2 W290C lies within the Ig-like C2-type domain 3 of the Fgfr2 protein (UniProt.org). W290C does not result in increased Fgfr2 phosphorylation, but increases both ligand-dependent and ligand-independent dimerization of Fgfr2 (PMID: 23786770), results in a growth advantage relative to wild-type Fgfr2 in a competition assay (PMID: 34272467), is transforming in cell culture (PMID: 23786770, PMID: 34272467), and promotes tumor formation in xenograft models (PMID: 23786770). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR2 mutant FGFR2 act mut FGFR2 W290C FGFR2 mutant FGFR2 exon7 FGFR2 W290C |
Transcript | NM_000141.5 |
gDNA | chr10:g.121520048C>A |
cDNA | c.870G>T |
Protein | p.W290C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001144913 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_000141.5 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_022970 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_001320658.1 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_001144917.2 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_001144917.1 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_001144917 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_000141.4 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_022970.4 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_022970.3 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_000141 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_001320658.2 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
NM_001320658 | chr10:g.121520048C>A | c.870G>T | p.W290C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 W290C | Advanced Solid Tumor | sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, AZD4547 inhibited growth of transformed cells expressing FGFR2 W290C in culture (PMID: 23786770). | 23786770 |
FGFR2 W290C | Advanced Solid Tumor | sensitive | Infigratinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Truseltiq (infigratinib) inhibited growth of transformed cells expressing FGFR2 W290C in culture and inhibited tumor growth in xenograft models (PMID: 23786770). | 23786770 |
FGFR2 W290C | Advanced Solid Tumor | predicted - resistant | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 W290C were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR2 W290C | Advanced Solid Tumor | sensitive | Lenvatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lenvima (lenvatinib) inhibited growth of transformed cells expressing FGFR2 W290C in culture (PMID: 23786770). | 23786770 |
FGFR2 W290C | Advanced Solid Tumor | sensitive | Pazopanib | Preclinical - Cell culture | Actionable | In a preclinical study, Votrient (pazopanib) inhibited growth of transformed cells expressing FGFR2 W290C in culture (PMID: 23786770). | 23786770 |
FGFR2 W290C | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited growth of transformed cells expressing FGFR2 W290C in culture (PMID: 23786770). | 23786770 |
FGFR2 W290C | Advanced Solid Tumor | sensitive | Cediranib | Preclinical - Cell culture | Actionable | In a preclinical study, Cediranib (AZD-2171) inhibited growth of transformed cells expressing FGFR2 W290C in culture (PMID: 23786770). | 23786770 |
FGFR2 W290C | Advanced Solid Tumor | predicted - sensitive | Erdafitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 W290C were sensitive to treatment with Balversa (erdafitinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 W290C | intrahepatic cholangiocarcinoma | predicted - sensitive | Futibatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Lytgobi (futibatinib) treatment at a dose of 20mg led to an objective response rate of 15.6% (10/64) and a median progression-free survival of 5.1 months in patients with cholangiocarcinoma harboring FGF or FGFR 1-4 alterations, including a partial response with a progression-free survival of 12.7 months and a duration of response of 9.9 months in an intrahepatic cholantiocarcinoma patient harboring FGFR2 W290C (PMID: 34551969; NCT02052778). | 34551969 |
FGFR2 W290C | Advanced Solid Tumor | predicted - sensitive | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 W290C were sensitive to treatment with Lytgobi (futibatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 W290C | Advanced Solid Tumor | predicted - sensitive | Pemigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 W290C were sensitive to treatment with Pemazyre (pemigatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 W290C | Advanced Solid Tumor | predicted - sensitive | E7090 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 W290C were sensitive to treatment with E7090 in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |