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| Gene | FGFR2 |
| Variant | K660N |
| Impact List | missense |
| Protein Effect | gain of function |
| Gene Variant Descriptions | FGFR2 K660N (corresponds to K559N in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). K660N confers a gain of function to the Fgfr2 protein, as demonstrated by increased autophosphorylation, increased phosphorylation of FRS2, and increased activation of Mek1/2 and Stat3, upon FGF1 stimulation, and as compared to wild-type Fgfr2 in cell culture (PMID: 23527311). |
| Associated Drug Resistance | |
| Category Variants Paths |
FGFR2 mutant FGFR2 act mut FGFR2 K660N |
| Transcript | NM_022970.4 |
| gDNA | chr10:g.121488000C>G |
| cDNA | c.1980G>C |
| Protein | p.K660N |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| NM_022970.3 | chr10:g.121488000C>G | c.1980G>C | p.K660N | RefSeq | GRCh38/hg38 |
| NM_022970 | chr10:g.121488000C>G | c.1980G>C | p.K660N | RefSeq | GRCh38/hg38 |
| NM_022970.4 | chr10:g.121488000C>G | c.1980G>C | p.K660N | RefSeq | GRCh38/hg38 |
| NM_001144913 | chr10:g.121488000C>G | c.1980G>C | p.K660N | RefSeq | GRCh38/hg38 |
| NM_001144913.1 | chr10:g.121488000C>G | c.1980G>C | p.K660N | RefSeq | GRCh38/hg38 |
| NM_001144913.1 | chr10:g.121488000C>G | c.1980G>C | p.K660N | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| FGFR2 K660N | Advanced Solid Tumor | sensitive | PRN1371 | Preclinical - Cell culture | Actionable | In a preclinical study, PRN1371 inhibited proliferation of transformed cells over expressing FGFR2 K660N in culture (PMID: 28978721). | 28978721 detail... |
| FGFR2 K660N | Advanced Solid Tumor | sensitive | Infigratinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Truseltiq (infigratinib) inhibited growth of transformed cells expressing FGFR2 K660N in culture and inhibited tumor growth in xenograft models (PMID: 23786770). | 23786770 |
| FGFR2 K660N | Advanced Solid Tumor | sensitive | Ponatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited growth of transformed cells expressing FGFR2 K660N in culture (PMID: 23786770). | 23786770 |
| FGFR2 K660N | Advanced Solid Tumor | sensitive | Pazopanib | Preclinical - Cell culture | Actionable | In a preclinical study, Votrient (pazopanib) inhibited growth of transformed cells expressing FGFR2 K660N in culture (PMID: 23786770). | 23786770 |
| FGFR2 K660N | Advanced Solid Tumor | sensitive | Cediranib | Preclinical - Cell culture | Actionable | In a preclinical study, Cediranib (AZD-2171) inhibited growth of transformed cells expressing FGFR2 K660N in culture (PMID: 23786770). | 23786770 |
| FGFR2 K660N | Advanced Solid Tumor | sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Fexagratinib (AZD4547) inhibited growth of transformed cells expressing FGFR2 K660N in culture (PMID: 23786770). | 23786770 |
| FGFR2 K660N | Advanced Solid Tumor | sensitive | Lenvatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Lenvima (lenvatinib) inhibited growth of transformed cells expressing FGFR2 K660N in culture (PMID: 23786770). | 23786770 |
| FGFR2 K660N | breast cancer | sensitive | Fexagratinib + Fulvestrant | Preclinical - Cell culture | Actionable | In a preclinical study, Fexagratinib (AZD4547) and Faslodex (fulvestrant) combination treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 K660N in culture (PMID: 32723837). | 32723837 |
| FGFR2 K660N | estrogen-receptor positive breast cancer | sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Fexagratinib (AZD4547) treatment decreased viability of ESR1-positive breast cancer cells expressing FGFR2 K660N in culture (PMID: 32723837). | 32723837 |
| FGFR2 K660N | 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 K660N in culture (PMID: 32723837). | 32723837 |
| FGFR2 K660N | 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 K660N in culture (PMID: 32723837). | 32723837 |
| FGFR2 K660N | 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 K660N in culture (PMID: 32723837). | 32723837 |
| FGFR2 K660N | 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 K660N in culture (PMID: 32723837). | 32723837 |
| FGFR2 K660N | Advanced Solid Tumor | predicted - sensitive | TYRA-200 | Preclinical - Cell culture | Actionable | In a preclinical study, TYRA-200 demonstrated activity in cells expressing FGFR2 K660N in culture (Eur J Cancer 2022 Vol 174, Supp 1:S16). | detail... |