Abstract
Abstract Small cell cancers are aggressive tumors with unfavorable prognosis. Small cell bladder carcinomas are a particularly troublesome and poorly differentiated tumor where little is known and in which few targeted therapeutic options exist for molecularly defined patients. We therefore sought to characterize both common and actionable aberrant pathways in small cell bladder tumors to serve as a guide for therapeutic development. Utilizing a combination of deep targeted capture and whole-genome sequencing approaches, we characterized the mutational and DNA copy number alteration spectrum of twenty patients with small-cell bladder cancer including multi-region profiling of a subset of cases with mixed small cell and urothelial histologies. Integrating molecular, clinical, and pathway data along with comparative genomic analyses of 371 urothelial bladder and small cell lung cancers, we identified histology- and lineage-specific lesions and significant differences in the prevalence of specific pathway aberrations. Whole-genome sequencing revealed structurally complex tumors and, in some cases, somatic hypermutation, including one sample harboring more than 150,000 clonal mutations. Aberrations in G1/S cell cycle progression appear to be pathognomonic in small cell tumors. Furthermore, additional lesions affecting both pro/anti apoptotic as well as metabolic pathways occurred in patterns that are distinct from other small-cell and bladder cancers. In total, 85% of small cell bladder cancer samples contain at least one potentially clinically actionable lesion. These results indicate that integrative genomic analyses of small-cell bladder cancer facilitates therapeutic development and pathway targeting in a complex mutational landscape. Citation Format: Matthew T. Chang, Saurabh Asthana, Gopakumar Iyer, Neil Desai, Hikmat Al-Ahmadie, Jocelyn Chapman, Bernard H. Bochner, Jonathan E. Rosenberg, Dean F. Bajorin, David B. Solit, Barry S. Taylor. The landscape of actionable genomic lesions in small cell bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-316. doi:10.1158/1538-7445.AM2014-LB-316
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
