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ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors

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dc.contributor.author Balbás Martínez, Cristina
dc.contributor.author Rodríguez Pinilla, María
dc.contributor.author Casanova, Ariel
dc.contributor.author Domínguez, Orlando
dc.contributor.author Pisano, David G.
dc.contributor.author Gómez López, Gonzalo
dc.contributor.author Lloreta Trull, Josep, 1958-
dc.contributor.author Lorente Garin, José Antonio
dc.contributor.author Malats i Riera, Núria
dc.contributor.author Real, Francisco X.
dc.date.accessioned 2015-05-13T10:42:02Z
dc.date.available 2015-05-13T10:42:02Z
dc.date.issued 2013
dc.identifier.citation Balbas-Martínez C, Rodríguez-Pinilla M, Casanova A, Domínguez O, Pisano DG, Gómez G et al. ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors. PLoS ONE. 2013;8(5):e62483. DOI: 10.1371/journal.pone.0062483
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/23572
dc.description.abstract Urothelial bladder cancer (UBC) is heterogeneous at the clinical, pathological, genetic, and epigenetic levels. Exome sequencing has identified ARID1A as a novel tumor suppressor gene coding for a chromatin remodeling protein that is mutated in UBC. Here, we assess ARID1A alterations in two series of patients with UBC. In the first tumor series, we analyze exons 2–20 in 52 primary UBC and find that all mutant tumors belong to the aggressive UBC phenotype (high grade non-muscle invasive and muscle invasive tumors) (P = 0.05). In a second series (n = 84), we assess ARID1A expression using immunohistochemistry, a surrogate for mutation analysis, and find that loss of expression increases with higher stage/grade, it is inversely associated with FGFR3 overexpression (P = 0.03) but it is not correlated with p53 overexpression (P = 0.30). We also analyzed the expression of cytokeratins in the same set of tumor and find, using unsupervised clustering, that tumors with ARID1A loss of expression are generally KRT5/6-low. In this patient series, loss of ARID1A expression is also associated with worse prognosis, likely reflecting the higher prevalence of losses found in tumors of higher stage and grade. The independent findings in these two sets of patients strongly support the notion that ARID1A inactivation is a key player in bladder carcinogenesis occurring predominantly in FGFR3 wild type tumors.
dc.description.sponsorship This work was supported in part by grant Consolider ONCOBIO from Ministerio de Economía y Competitividad, Spain; grants 00/0745, PI051436, PI061614, G03/174 and Red Temática de Investigación Cooperativa en Cáncer (grant RD06/0020-RTICC) from Instituto de Salud Carlos III; Asociación Española Contra el Cáncer; and EU FP7 grant agreement numbers 201663 (UROMOL) and 201333 (DECANBIO). CBM is recipient of a La Caixa International PhD Fellowship
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science (PLoS)
dc.relation.ispartof PLoS ONE. 2013;8(5):e62483
dc.rights © 2013 Balbás-Martínez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
dc.subject.other Fetge -- Càncer
dc.subject.other Proteïnes
dc.title ARID1A alterations are associated with FGFR3-wild type, poor-prognosis, urothelial bladder tumors
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0062483
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/201663
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/201333
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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