Dysregulation of EMT Drives the Progression to Clinically Aggressive Sarcomatoid Bladder Cancer.
Cell Rep
; 27(6): 1781-1793.e4, 2019 05 07.
Article
em En
| MEDLINE
| ID: mdl-31067463
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.
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Base de dados:
MEDLINE
Assunto principal:
Sarcoma
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Neoplasias da Bexiga Urinária
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Progressão da Doença
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Transição Epitelial-Mesenquimal
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article