The origin of bladder cancer from mucosal field effects

Jolanta Bondaruk; Roman Jaksik; Ziqiao Wang; David Cogdell; Sangkyou Lee; Yujie Chen; Khanh Ngoc Dinh; Tadeusz Majewski; Li Zhang; Shaolong Cao; Feng Tian; Hui Yao; Paweł Kuś; Huiqin Chen; John N Weinstein; Neema Navai; Colin Dinney; Jianjun Gao; Dan Theodorescu; Christopher Logothetis; Charles C Guo; Wenyi Wang; David McConkey; Peng Wei; Marek Kimmel; Bogdan Czerniak

doi:10.1016/j.isci.2022.104551

The origin of bladder cancer from mucosal field effects

iScience. 2022 Jun 7;25(7):104551. doi: 10.1016/j.isci.2022.104551. eCollection 2022 Jul 15.

Authors

Jolanta Bondaruk¹, Roman Jaksik², Ziqiao Wang³, David Cogdell¹, Sangkyou Lee¹, Yujie Chen⁴, Khanh Ngoc Dinh⁵, Tadeusz Majewski¹, Li Zhang⁶, Shaolong Cao³, Feng Tian⁷, Hui Yao³, Paweł Kuś², Huiqin Chen⁷, John N Weinstein⁷, Neema Navai⁸, Colin Dinney⁸, Jianjun Gao⁹, Dan Theodorescu¹⁰, Christopher Logothetis⁹, Charles C Guo¹, Wenyi Wang⁷, David McConkey¹¹, Peng Wei³, Marek Kimmel¹², Bogdan Czerniak¹

Affiliations

¹ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
² Department of Systems Biology and Engineering and Biotechnology Centre, Silesian University of Technology, Gliwice, Poland.
³ Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁴ Systems, Synthetic and Physical Biology Program, Rice University, Houston, TX, USA.
⁵ Department of Statistics and the Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA.
⁶ Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
⁷ Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁸ Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁹ Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, TX, USA.
¹⁰ Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai, Los Angeles, CA, USA.
¹¹ Johns Hopkins Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD, USA.
¹² Department of Statistics, Rice University, Houston, TX, USA.

Abstract

Whole-organ mapping was used to study molecular changes in the evolution of bladder cancer from field effects. We identified more than 100 dysregulated 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 α mutations occurred at low frequencies while the β 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 β mutations.

Keywords: Cancer; Cell biology; Molecular biology.

Abstract

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