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Gene | FGFR2 |
Variant | Y375C |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | FGFR2 Y375C lies within the extracellular juxtamembrane domain of the Fgfr2 protein (PMID: 17525745). Y375C results in proliferation similar to wild-type Fgfr2 in a competition assay and transformation activity similar to wild-type in cultured cells (PMID: 34272467), but constitutive phosphorylation of Fgfr2 in cell culture, activation of Mapk p38 signaling, and abnormal proliferation and differentiation in the skin and skull of transgenic mouse models (PMID: 22585574). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR2 mutant FGFR2 act mut FGFR2 Y375C |
Transcript | NM_000141.5 |
gDNA | chr10:g.121515280T>C |
cDNA | c.1124A>G |
Protein | p.Y375C |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_000141.4 | chr10:g.121515280T>C | c.1124A>G | p.Y375C | RefSeq | GRCh38/hg38 |
NM_000141 | chr10:g.121515280T>C | c.1124A>G | p.Y375C | RefSeq | GRCh38/hg38 |
NM_001320658.1 | chr10:g.121515280T>C | c.1124A>G | p.Y375C | RefSeq | GRCh38/hg38 |
NM_001320658.2 | chr10:g.121515280T>C | c.1124A>G | p.Y375C | RefSeq | GRCh38/hg38 |
NM_000141.5 | chr10:g.121515280T>C | c.1124A>G | p.Y375C | RefSeq | GRCh38/hg38 |
NM_001320658 | chr10:g.121515280T>C | c.1124A>G | p.Y375C | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR2 Y375C | breast cancer | sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, AZD4547 inhibited viability of breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453). | 37980453 |
FGFR2 Y375C | Advanced Solid Tumor | predicted - sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 Y375C were sensitive to treatment with AZD4547 in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 Y375C | Advanced Solid Tumor | predicted - sensitive | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 Y375C were sensitive to treatment with Truseltiq (infigratinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 Y375C | breast cancer | sensitive | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dovitinib (TKI258) inhibited viability of breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453). | 37980453 |
FGFR2 Y375C | Advanced Solid Tumor | predicted - resistant | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 Y375C were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
FGFR2 Y375C | endometrial 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 6.9 months in a patient with endometrial cancer harboring FGFR2 Y375C (PMID: 37541273; NCT04083976). | 37541273 |
FGFR2 Y375C | breast cancer | sensitive | Erdafitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Balversa (erdafitinib) inhibited viability of breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453). | 37980453 |
FGFR2 Y375C | salivary gland cancer | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a complete response with a duration of response of 5.75 months in one patient and a partial response with a duration of response of 13.47 months in another patient, both with salivary gland cancer harboring FGFR2 Y375C (PMID: 37541273; NCT04083976). | 37541273 |
FGFR2 Y375C | lung non-squamous non-small cell carcinoma | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a complete response with a duration of response of 5.59 months in a patient with non-squamous non-small cell lung cancer harboring FGFR2 Y375C (PMID: 37541273; NCT04083976). | 37541273 |
FGFR2 Y375C | Advanced Solid Tumor | predicted - sensitive | Erdafitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 Y375C were sensitive to treatment with Balversa (erdafitinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 Y375C | breast cancer | sensitive | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lytgobi (futibatinib) inhibited Fgfr2 signaling and viability in breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453). | 37980453 |
FGFR2 Y375C | 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 35.5 months and a best objective response of -45% in a patient with intrahepatic cholangiocarcinoma harboring FGFR2 Y375C (reported as Y376C) (PMID: 39226398). | 39226398 |
FGFR2 Y375C | cholangiocarcinoma | sensitive | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lytgobi (futibatinib) inhibited viability of a cholangiocyte cell line harboring FGFR2 Y375C in culture (PMID: 37980453). | 37980453 |
FGFR2 Y375C | Advanced Solid Tumor | predicted - sensitive | Futibatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 Y375C were sensitive to treatment with Lytgobi (futibatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 Y375C | breast cancer | sensitive | Pemigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Pemazyre (pemigatinib) inhibited viability of breast epithelial cells expressing FGFR2 Y375C in culture (PMID: 37980453). | 37980453 |
FGFR2 Y375C | Advanced Solid Tumor | predicted - sensitive | Pemigatinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 Y375C were sensitive to treatment with Pemazyre (pemigatinib) in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 Y375C | Advanced Solid Tumor | predicted - sensitive | E7090 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR2 Y375C were sensitive to treatment with E7090 in culture, demonstrating reduced cell viability (PMID: 34272467). | 34272467 |
FGFR2 Y375C | salivary gland carcinoma | predicted - sensitive | Lirafugratinib | Case Reports/Case Series | Actionable | In a Phase I/II trial (ReFocus), Lirafugratinib treatment resulted in a partial response with near complete resolution of liver metastases, and regression of lung and adrenal metastases in a patient with metastatic carcinoma of the right parotid salivary gland harboring FGFR2 Y375C (PMID: 37270847; NCT04526106). | 37270847 |