Περίληψη:
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.
Συγγραφείς:
Balbas-Martinez, Cristina
Sagrera, Ana
Carrillo-de-Santa-Pau,
Enrique
Earl, Julie
Marquez, Mirari
Vazquez, Miguel and
Lapi, Eleonora
Castro-Giner, Francesc
Beltran, Sergi
Bayes,
Monica
Carrato, Alfredo
Cigudosa, Juan C.
Dominguez, Orlando
and Gut, Marta
Herranz, Jesus
Juanpere, Nuria
Kogevinas,
Manolis
Langa, Xavier
Lopez-Knowles, Elena
Lorente, Jose A.
and Lloreta, Josep
Pisano, David G.
Richart, Laia
Rico,
Daniel
Salgado, Rocio N.
Tardon, Adonina
Chanock, Stephen
and Heath, Simon
Valencia, Alfonso
Losada, Ana
Gut, Ivo and
Malats, Nuria
Real, Francisco X.
