FGFR2 W290C: Gene Variant Detail - Cancer Knowledgebase (CKB)

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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

Variant Reference Transcript
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Transcript	NM_000141.5
gDNA	chr10:g.121520048C>A
cDNA	c.870G>T
Protein	p.W290C
Source Database	RefSeq
Genome Build	GRCh38/hg38

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Transcript	gDNA	cDNA	Protein	Source Database	Genome Build
NM_000141	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_000141.5	chr10:g.121520048C>A	c.870G>T	p.W290C	RefSeq	GRCh38/hg38
NM_001144913	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_001144913.1	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_001144917.1	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_001320658	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_001320658.2	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_022970.3	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

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Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
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	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	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	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	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	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	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	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
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	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 - 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

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FGFR2 W290CGene Variant Detail

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FGFR2 W290C
Gene Variant Detail