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

Abstract

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. 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.

• Authors: Cristina Balbás-Martínez, Ana Sagrera, Enrique Carrillo-de-Santa-Pau, Julie Earl, Mirari Márquez, Miguel Vazquez, Eleonora Lapi, Francesc Castro-Giner, Sergi Beltran, Mònica Bayés, Alfredo Carrato, Juan C Cigudosa, Orlando Domínguez, Marta Gut, Jesús Herranz, Núria Juanpere, Manolis Kogevinas, Xavier Langa, Elena López-Knowles, José A Lorente, Josep Lloreta, David G Pisano, Laia Richart, Daniel Rico, Rocío N Salgado, Adonina Tardón, Stephen Chanock, Simon Heath, Alfonso Valencia, Ana Losada, Ivo Gut, Núria Malats, Francisco X Real
• Journal: Nature genetics (Nat Genet) Vol. 45 Issue 12 Pg. 1464-9 (Dec 2013) ISSN: 1546-1718 [Electronic] United States
• PMID: 24121791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Nuclear
• Cell Cycle Proteins
• STAG2 protein, human

Topics

• Adult
• Aneuploidy
• Antigens, Nuclear (genetics)
• Carcinoma (genetics, pathology)
• Cell Cycle Proteins
• Cell Division (genetics)
• Cell Line, Tumor
• Chromatin Assembly and Disassembly (genetics)
• DNA Repair (genetics)
• Gene Frequency
• Gene Silencing
• Genes, Tumor Suppressor
• Humans
• Mutation
• Urinary Bladder Neoplasms (genetics, pathology)