TY - JOUR
TI - Recurrent inactivation of STAG2 in bladder cancer is not associated with
aneuploidy
AU - Balbas-Martinez, Cristina
AU - Sagrera, Ana
AU - Carrillo-de-Santa-Pau,
AU - Enrique
AU - Earl, Julie
AU - Marquez, Mirari
AU - Vazquez, Miguel and
AU - Lapi, Eleonora
AU - Castro-Giner, Francesc
AU - Beltran, Sergi
AU - Bayes,
AU - Monica
AU - Carrato, Alfredo
AU - Cigudosa, Juan C.
AU - Dominguez, Orlando
AU - and Gut, Marta
AU - Herranz, Jesus
AU - Juanpere, Nuria
AU - Kogevinas,
AU - Manolis
AU - Langa, Xavier
AU - Lopez-Knowles, Elena
AU - Lorente, Jose A.
AU - and Lloreta, Josep
AU - Pisano, David G.
AU - Richart, Laia
AU - Rico,
AU - Daniel
AU - Salgado, Rocio N.
AU - Tardon, Adonina
AU - Chanock, Stephen
AU - and Heath, Simon
AU - Valencia, Alfonso
AU - Losada, Ana
AU - Gut, Ivo and
AU - Malats, Nuria
AU - Real, Francisco X.
JO - Nature Genetics
PY - 2013
VL - 45
TODO - 12
SP - 1464-U221
PB - Nature Publishing Group
SN - 1061-4036, 1546-1718
TODO - 10.1038/ng.2799
TODO - null
TODO - 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.
ER -