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

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Date
2013-12-01
Author
Balbás-Martínez, C
Sagrera, A
Carrillo-de-Santa-Pau, E
Earl, J
Márquez, M
Vazquez, M
Lapi, E
Castro-Giner, F
Beltran, S
Bayés, M
Carrato, A
Cigudosa, JC
Domínguez, O
Gut, M
Herranz, J
Juanpere, N
Kogevinas, M
Langa, X
López-Knowles, E
Lorente, JA
Lloreta, J
Pisano, DG
Richart, L
Rico, D
Salgado, RN
Tardón, A
Chanock, S
Heath, S
Valencia, A
Losada, A
Gut, I
Malats, N
Real, FX
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Type
Journal Article
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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.
URI
https://repository.icr.ac.uk/handle/internal/5274
DOI
https://doi.org/10.1038/ng.2799
https://doi.org/10.1038/ng.2799
 
Collections
  • Breast Cancer Research
Subject
Adult
Aneuploidy
Antigens, Nuclear
Carcinoma
Cell Cycle Proteins
Cell Division
Cell Line, Tumor
Chromatin Assembly and Disassembly
DNA Repair
Gene Frequency
Gene Silencing
Genes, Tumor Suppressor
Humans
Mutation
Urinary Bladder Neoplasms
Language
eng
Date accepted
2013-09-16
License start date
2013-12-01
Citation
Nature Genetics, 2013, 45 (12), pp. 1464 - 1469
Publisher
NATURE PUBLISHING GROUP

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