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Gene | FGFR2 |
Variant | C382R |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR2 C382R (also referred to as C383R) lies within the helical domain of the Fgfr2 protein (UniProt.org). C382R results in proliferation similar to wild-type Fgfr2 in a competition assay (PMID: 34272467), but confers a gain of function on the Fgfr2 protein, as demonstrated by constitutive MAPK pathway activation (PMID: 24993163), and transformation of cells in culture (PMID: 24993163, PMID: 34272467). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR2 mutant FGFR2 act mut FGFR2 C382R |
Transcript | NM_000141.5 |
gDNA | chr10:g.121515260A>G |
cDNA | c.1144T>C |
Protein | p.C382R |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_001320658.2 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_001320658 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_001320658.1 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_000141 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_000141.5 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
NM_000141.4 | chr10:g.121515260A>G | c.1144T>C | p.C382R | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 C382R | breast cancer | predicted - sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, AZD4547 inhibited growth of mouse mammary epithelial cells expressing FGFR2 C287R (corresponding to C382R in human) in culture (PMID: 35948633). | 35948633 |
FGFR2 C382R | Advanced Solid Tumor | predicted - sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 C382R were sensitive to treatment with AZD4547 in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 C382R | cholangiocarcinoma | no benefit | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) did not decrease viability of a cholangiocarcinoma cell line expressing FGFR2 C382R in culture (PMID: 37964396). | 37964396 |
FGFR2 C382R | Advanced Solid Tumor | predicted - sensitive | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 C382R were sensitive to treatment with Truseltiq (infigratinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 C382R | Advanced Solid Tumor | predicted - resistant | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 C382R were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR2 C382R | endometrial cancer | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in partial response in two patients with endometrial cancer harboring FGFR2 C382R, with a duration of response of 23.72 months and 2.79 months, respectively (PMID: 37541273; NCT04083976). | 37541273 |
FGFR2 C382R | breast cancer | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 14.32 months in a patient with breast cancer harboring FGFR2 C382R (PMID: 37541273; NCT04083976). | 37541273 |
FGFR2 C382R | intrahepatic cholangiocarcinoma | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a clinical case study, Balversa (erdafitinib) treatment resulted in a partial response with a progression-free survival of 9.3 months and best objective response of -67% in a patient with intrahepatic cholangiocarcinoma harboring FGFR2 C382R (reported as C383R) (PMID: 39226398). | 39226398 |
FGFR2 C382R | cholangiocarcinoma | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 15.11 months in a patient with cholangiocarcinoma harboring FGFR2 C382R (PMID: 37541273; NCT04083976). | 37541273 |
FGFR2 C382R | head and neck squamous cell carcinoma | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 2.79 months in a patient with squamous cell head and neck cancer harboring FGFR2 C382R (PMID: 37541273; NCT04083976). | 37541273 |
FGFR2 C382R | triple-receptor negative breast cancer | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a clinical case study, Balversa (erdafitinib) treatment resulted in a partial response with a progression-free survival of 24.3 months and best objective response of -59% in a patient with a triple-negative breast cancer harboring FGFR2 C382R (reported as C383R) (PMID: 39226398). | 39226398 |
FGFR2 C382R | Advanced Solid Tumor | predicted - sensitive | Erdafitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 C382R were sensitive to treatment with Balversa (erdafitinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 C382R | intrahepatic cholangiocarcinoma | predicted - sensitive | Futibatinib | Case Reports/Case Series | Actionable | In a clinical case study, Lytgobi (futibatinib) treatment resulted in a partial response with a progression-free survival of 17.3 months and a best objective response of -53% in a patient with intrahepatic cholangiocarcinoma harboring FGFR2 C382R (reported as C383R) (PMID: 39226398). | 39226398 |
FGFR2 C382R | Advanced Solid Tumor | predicted - sensitive | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 C382R were sensitive to treatment with Lytgobi (futibatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 C382R | breast cancer | predicted - sensitive | Pemigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Pemazyre (pemigatinib) inhibited growth of mouse mammary epithelial cells expressing FGFR2 C287R (corresponding to C382R in human) in culture (PMID: 35948633). | 35948633 |
FGFR2 C382R | intrahepatic cholangiocarcinoma | predicted - sensitive | Pemigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Pemazyre (pemigatinib) treatment resulted in complete metabolic remission in a patient with metastatic intrahepatic cholangiocarcinoma harboring FGFR2 C382R (PMID: 36188486). | 36188486 |
FGFR2 C382R | cholangiocarcinoma | predicted - sensitive | Pemigatinib | Case Reports/Case Series | Actionable | In a Phase I trial (FIGHT-101), Pemazyre (pemigatinib) treatment led to a partial response in a cholangiocarcinoma patient harboring FGFR2 C382R (PMID: 35176457; NCT02393248). | 35176457 |
FGFR2 C382R | cholangiocarcinoma | predicted - sensitive | Pemigatinib | Case Reports/Case Series | Actionable | In a Phase II trial (FIGHT-207), Pemazyre (pemigatinib) treatment resulted in a partial response with a 49.7% decrease in target lesion and a progression-free survival of 6 months in a patient with cholangiocarcinoma harboring FGFR2 C382R (Cancer Res (2023) 83 (8_Supplement): CT016; NCT03822117). | detail... |
FGFR2 C382R | Advanced Solid Tumor | predicted - sensitive | Pemigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 C382R were sensitive to treatment with Pemazyre (pemigatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 C382R | cholangiocarcinoma | predicted - sensitive | Tinengotinib | Case Reports/Case Series | Actionable | In a Phase I trial, Tinengotinib (TT-00420) treatment was well tolerated and resulted in stable disease in 53.3% (23/43) and partial response in 16.3% (7/43) of patients with advanced solid tumors, including a partial response in a patient with cholangiocarcinoma harboring FGFR2 C382R (PMID: 38297981; NCT03654547). | 38297981 |