Cohesin mutations in human cancer

Abstract

Cohesin is a highly-conserved protein complex that plays important roles in sister chromatid cohesion, chromatin structure, gene expression, and DNA repair. In humans, cohesin is a ubiquitously expressed, multi-subunit protein complex composed of core subunits SMC1A, SMC3, RAD21, STAG1/2 and regulatory subunits WAPL, PDS5A/B, CDCA5, NIPBL, and MAU2. Recent studies have demonstrated that genes encoding cohesin subunits are somatically mutated in a wide range of human cancers. STAG2 is the most commonly mutated subunit, and in a recent analysis was identified as one of only 12 genes that are significantly mutated in four or more cancer types. In this review we summarize the findings reported to date and comment on potential functional implications of cohesin mutation in the pathogenesis of human cancer.

Keywords: Cancer; Cohesin; Ewing sarcoma; Myeloid malignancy; STAG2; Urothelial carcinoma.

Fig 1

Model of cohesion complex.

Fig 2

Diagram of the STAG2 protein with the locations of a representative subset of mutations that have been identified in human tumors. The mutations displayed are from refs. , –, –, , , , , . STAG2 stromal antigen domain. SQD, stromalin conserved domain.