iScience (Jul 2022)
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
Affiliations
- Jolanta Bondaruk
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Roman Jaksik
- Department of Systems Biology and Engineering and Biotechnology Centre, Silesian University of Technology, Gliwice, Poland
- Ziqiao Wang
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- David Cogdell
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Sangkyou Lee
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Yujie Chen
- Systems, Synthetic and Physical Biology Program, Rice University, Houston, TX, USA
- Khanh Ngoc Dinh
- Department of Statistics and the Irving Institute for Cancer Dynamics, Columbia University, New York, NY, USA
- Tadeusz Majewski
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Li Zhang
- Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA
- Shaolong Cao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Feng Tian
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Hui Yao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Paweł Kuś
- Department of Systems Biology and Engineering and Biotechnology Centre, Silesian University of Technology, Gliwice, Poland
- Huiqin Chen
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- John N. Weinstein
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Neema Navai
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Colin Dinney
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Jianjun Gao
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, TX, USA
- Dan Theodorescu
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai, Los Angeles, CA, USA
- Christopher Logothetis
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, TX, USA
- Charles C. Guo
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Wenyi Wang
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- David McConkey
- Johns Hopkins Greenberg Bladder Cancer Institute, Johns Hopkins University, Baltimore, MD, USA
- Peng Wei
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Marek Kimmel
- Department of Statistics, Rice University, Houston, TX, USA
- Bogdan Czerniak
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Corresponding author
- Journal volume & issue
-
Vol. 25,
no. 7
p. 104551
Abstract
Summary: 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.
