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

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. LorenteJosep 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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1464-1469
Number of pages6
JournalNature genetics
Volume45
Issue number12
DOIs
StatePublished - Dec 2013

ASJC Scopus subject areas

  • Genetics

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