Journal Article

Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy

López-Knowles, Elena, Márquez, Mirari, Lorente, José A, Lapi, Eleonora, Pisano, David G, Balbás-Martínez, Cristina, Kogevinas, Manolis, Herranz, Jesús, Real, Francisco X, Tardón, Adonina, Valencia, Alfonso, Castro-Giner, Francesc, Gut, Marta, Carrato, Alfredo, Domínguez, Orlando, Richart, Laia, Langa, Xavier, Carrillo-de-Santa-Pau, Enrique, Salgado, Rocío N, Bayés, Mònica, Beltran, Sergi, Cigudosa, Juan C, Malats, Núria, Sagrera, Ana, Rico, Daniel, Juanpere, Núria, Vazquez, Miguel, Lloreta, Josep, Losada, Ana, Gut, Ivo, Earl, Julie, Chanock, Stephen, Heath, Simon

2013

Overview

Francisco Real and colleagues report exome sequencing in urothelial bladder tumors. They show that STAG2 , a subunit of the cohesin complex, is recurrently mutated and provide evidence that STAG2 loss does not lead to increases in aneuploidy. Urothelial bladder cancer (UBC) is heterogeneous at the clinical, pathological and genetic levels. Tumor invasiveness (T) and grade (G) are the main factors associated with outcome and determine patient management 1 . A discovery exome sequencing screen ( n = 17), followed by a prevalence screen ( n = 60), identified new genes mutated in this tumor coding for proteins involved in chromatin modification ( MLL2 , ASXL2 and BPTF ), cell division ( STAG2 , SMC1A and SMC1B ) and DNA repair ( ATM , ERCC2 and FANCA ). STAG2 , a subunit of cohesin, was significantly and commonly mutated or lost in UBC, mainly in tumors of low stage or grade, and its loss was associated with improved outcome. Loss of expression was often observed in chromosomally stable tumors, and STAG2 knockdown in bladder cancer cells did not increase aneuploidy. STAG2 reintroduction in non-expressing cells led to reduced colony formation. Our findings indicate that STAG2 is a new UBC tumor suppressor acting through mechanisms that are different from its role in preventing aneuploidy.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/699/67/589/1336 / Adult / Agriculture / Aneuploidy / Animal Genetics and Genomics / Antigens, Nuclear - genetics / Biomedicine / Bladder cancer / Cancer Research / Carcinoma - genetics / Carcinoma - pathology / Cell cycle / Cell Cycle Proteins / Cell Division - genetics / Cell Line, Tumor / Chromatin Assembly and Disassembly - genetics / Deoxyribonucleic acid / DNA / DNA repair / DNA Repair - genetics / Exome sequencing / Gene expression / Gene Frequency / Gene Function / Gene mutations / Gene Silencing / Genes, Tumor Suppressor / Genetic aspects / Human Genetics / Humans / Identification and classification / Inactivation / letter / Library collections / Methods / Mutation / Reintroduction / Tumors / Urinary Bladder Neoplasms - genetics / Urinary Bladder Neoplasms - pathology