The origin of bladder cancer from mucosal field effects

被引：13

作者：

Bondaruk, Jolanta ^{[1
]}

Jaksik, Roman ^{[2
,3
]}

Wang, Ziqiao ^{[4
]}

Cogdell, David ^{[1
]}

Lee, Sangkyou ^{[1
]}

Chen, Yujie ^{[5
]}

Dinh, Khanh Ngoc ^{[6
,7
]}

Majewski, Tadeusz ^{[1
]}

Zhang, Li ^{[8
]}

Cao, Shaolong ^{[4
]}

Tian, Feng ^{[9
]}

Yao, Hui ^{[4
]}

Kus, Pawek ^{[2
,3
]}

Chen, Huiqin ^{[9
]}

Weinstein, John N.

Navai, Neema ^{[10
]}

Dinney, Colin

Gao, Jianjun ^{[11
]}

Theodorescu, Dan ^{[12
]}

Logothetis, Christopher ^{[11
]}

Guo, Charles C. ^{[1
]}

Wang, Wenyi ^{[9
]}

McConkey, David ^{[13
]}

Wei, Peng ^{[4
]}

Kimmel, Marek ^{[14
]}

Czerniak, Bogdan ^{[1
]}

机构：

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

[2] Silesian Tech Univ, Dept Syst Biol & Engn, Gliwice, Poland

[3] Silesian Tech Univ, Biotechnol Ctr, Gliwice, Poland

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

[5] Rice Univ, Syst Synthet & Phys Biol Program, Houston, TX USA

[6] Columbia Univ, Dept Stat, New York, NY USA

[7] Columbia Univ, Irving Inst Canc Dynam, New York, NY USA

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

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

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

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

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

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

[14] Rice Univ, Dept Stat, Houston, TX USA

来源：

ISCIENCE | 2022年 / 25卷 / 07期

关键词：

EPITHELIAL-MESENCHYMAL TRANSITION; TUMOR-SUPPRESSOR; CELLS; MIGRATION; SEQUENCE; MUTATION; IDENTIFICATION; PROGRESSION; ANNOTATION; ENRICHMENT;

D O I：

10.1016/j.isci.2022.104551

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：

Whole-organ mapping was used to study molecular changes in the evolution of bladder cancer from field effects. We identified more than 100 dysreglated pathways, involving immunity, differentiation, and transformation, as initiators of carcinogenesis. Dysregulation of interleukins signified the involvement of inflammation in the incipient phases of the process. An aberrant methylation/expression of multiple HOX genes signified dysregulation of the differentiation program. We identified three types of mutations based on their geographic distribution. The most common were mutations restricted to individual mucosal samples that targeted uroprogenitor cells. Two types of mutations were associated with clonal expansion and involved large areas of mucosa. The alpha mutations occurred at low frequencies while the beta mutations increased in frequency with disease progression. Modeling revealed that bladder carcinogenesis spans 10-15 years and can be divided into dormant and progressive phases. The progressive phase lasted 1-2 years and was driven by beta mutations.

引用

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