title: 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.affiliation: Epithelial Carcinogenesis Group, Molecular Pathology Programme, CNIO (Spanish National Cancer Research Centre), Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Balbás-Martínez
authors.forename: Ana
authors.initials: A
authors.lastname: Sagrera
authors.forename: Enrique
authors.initials: E
authors.lastname: Carrillo-de-Santa-Pau
authors.forename: Julie
authors.initials: J
authors.lastname: Earl
authors.forename: Mirari
authors.initials: M
authors.lastname: Márquez
authors.forename: Miguel
authors.initials: M
authors.lastname: Vazquez
authors.forename: Eleonora
authors.initials: E
authors.lastname: Lapi
authors.forename: Francesc
authors.initials: F
authors.lastname: Castro-Giner
authors.forename: Sergi
authors.initials: S
authors.lastname: Beltran
authors.forename: Mònica
authors.initials: M
authors.lastname: Bayés
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.forename: Juan C
authors.initials: JC
authors.lastname: Cigudosa
authors.forename: Orlando
authors.initials: O
authors.lastname: Domínguez
authors.forename: Marta
authors.initials: M
authors.lastname: Gut
authors.forename: Jesús
authors.initials: J
authors.lastname: Herranz
authors.forename: Núria
authors.initials: N
authors.lastname: Juanpere
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.forename: Xavier
authors.initials: X
authors.lastname: Langa
authors.forename: Elena
authors.initials: E
authors.lastname: López-Knowles
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
authors.forename: Josep
authors.initials: J
authors.lastname: Lloreta
authors.forename: David G
authors.initials: DG
authors.lastname: Pisano
authors.forename: Laia
authors.initials: L
authors.lastname: Richart
authors.forename: Daniel
authors.initials: D
authors.lastname: Rico
authors.forename: Rocío N
authors.initials: RN
authors.lastname: Salgado
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Simon
authors.initials: S
authors.lastname: Heath
authors.forename: Alfonso
authors.initials: A
authors.lastname: Valencia
authors.forename: Ana
authors.initials: A
authors.lastname: Losada
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
mesh_terms: D000328:Adult; D000782:Aneuploidy; D034961:Antigens, Nuclear / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D005787:Gene Frequency; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology; D000097722:Cohesins
chemical_list: D034961:Antigens, Nuclear; D018797:Cell Cycle Proteins; C508565:STAG2 protein, human; D000097722:Cohesins