FRAS1
Overview
FRAS1 encodes a large extracellular matrix protein involved in basement membrane integrity. Somatic mutations in FRAS1 are enriched in metastatic breast cancer relative to early breast cancer, where it forms part of an eight-gene prognostic signature associated with poor survival.
Alterations observed in the corpus
- Mutations more frequent in metastatic breast cancer (BRCA) vs early breast cancer (eBC) at FDR<0.01 (one of eight metastasis-enriched genes: ESR1, FSIP2, AGRN, FRAS1, IGFN1, EDC4, OSBPL3, PALB2) in 216 mBC whole-exome sequencing samples PMID:28027327.
- Patients with ≥1 mutation in the 8-gene metastatic-enrichment set had a 2-fold increase in death hazard (HR=1.97, 95% CI 1.34–2.89, p=0.001) on multivariate analysis PMID:28027327.
Cancer types (linked)
- BRCA — FRAS1 is part of the 8-gene metastasis-enriched mutation signature; prognostic significance requires independent validation PMID:28027327.
Co-occurrence and mutual exclusivity
- Co-enriched with ESR1, FSIP2, AGRN, IGFN1, EDC4, OSBPL3, and PALB2 as part of the metastasis-enriched mutation signature in mBC PMID:28027327.
Therapeutic relevance
- No direct therapeutic targeting reported in the corpus PMID:28027327.
Open questions
- Whether FRAS1 mutations drive metastatic spread or reflect passenger accumulation under therapy is not established; survival association was not corrected for mutational load PMID:28027327.
Sources
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