| Literature DB >> 27749842 |
Bishoy M Faltas1,2,3, Davide Prandi4, Scott T Tagawa1,2,3, Ana M Molina1,2, David M Nanus1,2,3, Cora Sternberg5, Jonathan Rosenberg6, Juan Miguel Mosquera1,7, Brian Robinson1,7, Olivier Elemento1,8,9, Andrea Sboner1,7,9, Himisha Beltran1,2,3, Francesca Demichelis1,4,9, Mark A Rubin1,3,7.
Abstract
Chemotherapy-resistant urothelial carcinoma has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 urothelial carcinoma samples, including 16 matched sets of primary and advanced tumors prospectively collected before and after chemotherapy. Our analysis provided several insights: (i) chemotherapy-treated urothelial carcinoma is characterized by intra-patient mutational heterogeneity, and the majority of mutations are not shared; (ii) both branching evolution and metastatic spread are very early events in the natural history of urothelial carcinoma; (iii) chemotherapy-treated urothelial carcinoma is enriched with clonal mutations involving L1 cell adhesion molecule (L1CAM) and integrin signaling pathways; and (iv) APOBEC-induced mutagenesis is clonally enriched in chemotherapy-treated urothelial carcinoma and continues to shape the evolution of urothelial carcinoma throughout its lifetime.Entities:
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Year: 2016 PMID： 27749842 PMCID： PMC5549141 DOI： 10.1038/ng.3692
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330