Frequent truncating mutations of the cohesin complex gene STAG2 in urothelial carcinoma of the bladder.

290 Background: We have recently identified the cohesin complex subunit STAG2 as a gene that is somatically mutated in human cancer and whose inactivation leads directly to chromosomal instability and aneuploidy (Solomon et al, Science, 2011 Aug 19). However, the complete tumor spectrum harboring STAG2 mutations and the clinical significance of STAG2 inactivation in cancer remain undefined. Methods: Immunohistochemistry was used to screen 2,214 tumors from each of the major tumor types for somatic loss of STAG2 expression. Sequencing of the STAG2 gene was performed on 111 urothelial carcinomas, and Affymetrix CytoscanHD Arrays were performed on STAG2 mutant tumors. Clinical data from 34 patients with non-muscle invasive urothelial carcinoma treated with transurethral resection and 349 patients with invasive urothelial carcinoma treated with radical cystectomy was correlated with tumor STAG2 status. Results: Complete loss of STAG2 expression was discovered in 52/295 urothelial carcinomas (18%), ranging fro...