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Supplementary Table S2 from Paired Exome Analysis Reveals Clonal Evolution and Potential Therapeutic Targets in Urothelial Carcinoma

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posted on 2023-03-31, 00:30 authored by Philippe Lamy, Iver Nordentoft, Karin Birkenkamp-Demtröder, Mathilde Borg Houlberg Thomsen, Palle Villesen, Søren Vang, Jakob Hedegaard, Michael Borre, Jørgen Bjerggaard Jensen, Søren Høyer, Jakob Skou Pedersen, Torben F. Ørntoft, Lars Dyrskjøt

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Lundbeck Foundation

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ARTICLE ABSTRACT

Greater knowledge concerning tumor heterogeneity and clonality is needed to determine the impact of targeted treatment in the setting of bladder cancer. In this study, we performed whole-exome, transcriptome, and deep-focused sequencing of metachronous tumors from 29 patients initially diagnosed with early-stage bladder tumors (14 with nonprogressive disease and 15 with progressive disease). Tumors from patients with progressive disease showed a higher variance of the intrapatient mutational spectrum and a higher frequency of APOBEC-related mutations. Allele-specific expression was also higher in these patients, particularly in tumor suppressor genes. Phylogenetic analysis revealed a common origin of the metachronous tumors, with a higher proportion of clonal mutations in the ancestral branch; however, 19 potential therapeutic targets were identified as both ancestral and tumor-specific alterations. Few subclones were present based on PyClone analysis. Our results illuminate tumor evolution and identify candidate therapeutic targets in bladder cancer. Cancer Res; 76(19); 5894–906. ©2016 AACR.

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