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

被引：83

作者：

Guo, Charles C. ^{[1
]}

Majewski, Tadeusz ^{[1
]}

Zhang, Li ^{[2
]}

Yao, Hui ^{[3
]}

Bondaruk, Jolanta ^{[1
]}

Wang, Yan ^{[1
]}

Zhang, Shizhen ^{[4
]}

Wang, Ziqiao ^{[1
]}

Lee, June Goo ^{[1
]}

Lee, Sangkyou ^{[1
]}

Cogdell, David ^{[1
]}

Zhang, Miao ^{[1
]}

Wei, Peng ^{[4
]}

Grossman, H. Barton ^{[5
]}

Kamat, Ashish ^{[5
]}

Duplisea, Jonathan James ^{[5
]}

Ferguson, James Edward, III ^{[5
]}

Huang, He ^{[1
]}

Dadhania, Vipulkumar ^{[1
]}

Gao, Jianjun ^{[6
]}

Dinney, Colin ^{[5
]}

Weinstein, John N. ^{[3
]}

Baggerly, Keith ^{[3
]}

McConkey, David ^{[7
]}

Czerniak, Bogdan ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[2] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA

[7] Johns Hopkins Univ, Johns Hopkins Greenberg Bladder Canc Inst, Baltimore, MD USA

来源：

CELL REPORTS | 2019年 / 27卷 / 06期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; UROTHELIAL CARCINOMA; MUTATIONAL PROCESSES; LUMINAL SUBTYPES; EXPRESSION; BREAST; PREDICTS; CHEMOTHERAPY; SIGNATURES; ALIGNMENT;

D O I：

10.1016/j.celrep.2019.04.048

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 muscleinvasive 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.

引用

页码：1781 / +

页数：17

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