FSIP2

Overview

FSIP2 (fibrous sheath interacting protein 2) is a large scaffold protein normally expressed in sperm flagella. Somatic mutations in FSIP2 are significantly enriched in metastatic breast cancer relative to early breast cancer and are part of an 8-gene prognostic signature associated with a 2-fold increase in death hazard.

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 — FSIP2 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, AGRN, FRAS1, 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 FSIP2 mutations are functional drivers of metastasis or reflect passenger accumulation is not established; the 8-gene survival association was not corrected for mutational load PMID:28027327.

Sources

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