| Literature DB >> 31067463 |
Charles C Guo1, Tadeusz Majewski1, Li Zhang2, Hui Yao3, Jolanta Bondaruk1, Yan Wang1, Shizhen Zhang1, Ziqiao Wang4, June Goo Lee1, Sangkyou Lee1, David Cogdell1, Miao Zhang1, Peng Wei4, H Barton Grossman5, Ashish Kamat5, Jonathan James Duplisea5, James Edward Ferguson5, He Huang1, Vipulkumar Dadhania1, Jianjun Gao6, Colin Dinney5, John N Weinstein3, Keith Baggerly3, David McConkey7, Bogdan Czerniak8.
Abstract
Sarcomatoid urothelial bladder cancer (SARC) displays a high propensity for distant metastasis and is associated with short survival. We report a comprehensive genomic analysis of 28 cases of SARC and 84 cases of conventional urothelial carcinoma (UC), with the TCGA cohort of 408 muscle-invasive bladder cancers serving as the reference. SARCs show a distinct mutational landscape, with enrichment of TP53, RB1, and PIK3CA mutations. They are related to the basal molecular subtype of conventional UCs and could be divided into epithelial-basal and more clinically aggressive mesenchymal subsets on the basis of TP63 and its target gene expression levels. Other analyses reveal that SARCs are driven by downregulation of homotypic adherence genes and dysregulation of the EMT network, and nearly half exhibit a heavily infiltrated immune phenotype. Our observations have important implications for prognostication and the development of more effective therapies for this highly lethal variant of bladder cancer.Entities:
Keywords: basal subtype; bladder cancer; chromatin remodeling; epithelial-mesenchymal transformation; genomic expression; immune phenotype; microRNA expression; molecular classification; sarcomatoid carcinoma; urothelial carcinoma
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Year: 2019 PMID： 31067463 PMCID： PMC6546434 DOI： 10.1016/j.celrep.2019.04.048
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423