Urothelial-to-Neural Plasticity Drives Progression to Small Cell Bladder Cancer

被引：23

作者：

Yang, Guoliang ^{[1
]}

Bondaruk, Jolanta ^{[1
]}

Cogdell, David ^{[1
]}

Wang, Ziqiao ^{[2
]}

Lee, Sangkyou ^{[1
]}

Lee, June Goo ^{[1
]}

Zhang, Shizhen ^{[1
]}

Choi, Woonyoung ^{[3
]}

Wang, Yan ^{[1
]}

Liang, Yu ^{[1
]}

Wang, Gang ^{[1
]}

Wang, Ying ^{[2
]}

Yao, Hui ^{[4
]}

Dadhania, Vipulkumar ^{[1
]}

Gao, Jianjun ^{[5
]}

Logothetis, Christopher ^{[5
]}

Siefker-Radtke, Arlene ^{[5
]}

Kamat, Ashish ^{[6
]}

Dinney, Colin ^{[6
]}

Theodorescu, Dan ^{[7
]}

Kimmel, Marek ^{[8
]}

Wei, Peng ^{[2
]}

Guo, Charles C. ^{[1
]}

Weinstein, John N. ^{[4
]}

McConkey, David J. ^{[3
]}

Czerniak, Bogdan ^{[1
]}

机构：

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

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

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

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

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

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

[7] Cedars Sinai, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA USA

[8] Rice Univ, Dept Stat, Houston, TX 77251 USA

来源：

ISCIENCE | 2020年 / 23卷 / 06期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; INFILTRATING IMMUNE CELLS; MOLECULAR CLASSIFICATION; LUMINAL SUBTYPES; CARCINOMA; BREAST; EXPRESSION; BASAL; IDENTIFICATION; DYSREGULATION;

D O I：

10.1016/j.isci.2020.101201

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We report a comprehensive molecular analysis of 34 cases of small cell carcinoma (SCC) and 84 cases of conventional urothelial carcinoma (UC), with The Cancer GenomeAtlas cohort of 408 conventional UCbladder cancers used as the reference. SCCs showed mutational landscapes characterized by nearly uniforminactivation of TP53 and were dominated by Sanger mutation signature 3 associated with loss of BRCA1/2 function. SCCs were characterized by downregulation of luminal and basal markers and were referred to as double-negative. Transcriptome analyses indicated that SCCs displayed lineage plasticity driven by a urothelial-to-neural phenotypic switch with a dysregulated epithelial-to-mesenchymal transition network. SCCs were depleted of immune cells, and expressed high levels of the immune checkpoint receptor, adenosine receptor A2A(ADORA2A), which is a potent inhibitor o fimmune infiltration. Our observations have important implications for the prognostication and development of more effective therapies for this lethal bladder cancer variant.

引用

页数：35

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