Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer.

Adult Aged Aged, 80 and over Disease Progression Epithelial-Mesenchymal Transition / genetics Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Regulatory Networks Humans Male MicroRNAs / genetics Middle Aged Mutagenesis / genetics Mutation / genetics Neoplasm Invasiveness Sarcoma / genetics Transcription, Genetic Urinary Bladder Neoplasms / genetics

basal subtype bladder cancer chromatin remodeling epithelial-mesenchymal transformation genomic expression immune phenotype microRNA expression molecular classification sarcomatoid carcinoma urothelial carcinoma

Journal

Cell reports

ISSN: 2211-1247

Titre abrégé: Cell Rep

Pays: United States

ID NLM: 101573691

Informations de publication

Date de publication:
07 05 2019

Historique:

received: 27 09 2018

revised: 28 02 2019

accepted: 10 04 2019

entrez: 9 5 2019

pubmed: 9 5 2019

medline: 2 7 2020

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2019.04.048 PMID: 31067463 PMC: PMC6546434

pubmed: 31067463

pii: S2211-1247(19)30521-2

doi: 10.1016/j.celrep.2019.04.048

pmc: PMC6546434

mid: NIHMS1528840

pii:

doi:

Substances chimiques

MicroRNAs 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

Pagination

1781-1793.e4

Subventions

Organisme : NCI NIH HHS

ID : P30 CA016672

Pays : United States

Organisme : NCI NIH HHS

ID : P50 CA091846

Pays : United States

Informations de copyright

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