The UBC-40 urothelial bladder cancer cell line index: a genomic resource for functional studies

Autor: Alfonso Valencia, Stephen J. Chanock, Luis A. Pérez-Jurado, H. B. Grossman, Julie Earl, Benjamín Rodríguez-Santiago, Wolfgang A. Schulz, Daniel Rico, Enrique Carrillo-de-Santa-Pau, Alfredo Carrato, David G. Pisano, Marinela Méndez-Pertuz, Herbert Auer, Francisco X. Real, Dan Theodorescu, Gonzalo Gomez
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: BMC Genomics
Recercat. Dipósit de la Recerca de Catalunya
instname
Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
Popis: Background. Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression./nResults. Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events./nConclusions. Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing. This work was supported, in part, by grants Consolider ONCOBIO, SAF2011-15934-E, Red Temática de Investigación Cooperativa en Cáncer (RTICC)]; Asociación Española Contra el Cáncer, EU-FP7-201663, and NIH RO-1 (CA089715); and National Institutes of Health grants CA075115 and CA104106 (to D.T.).
Databáze: OpenAIRE