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

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 LogothetisCharles C. Guo, Wenyi Wang, David McConkey, Peng Wei, Marek Kimmel, Bogdan Czerniak

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Article number	104551
Journal	iScience
Volume	25
Issue number	7
DOIs	https://doi.org/10.1016/j.isci.2022.104551
State	Published - Jul 15 2022

Keywords

Cancer
Cell biology
Molecular biology

ASJC Scopus subject areas

General

MD Anderson CCSG core facilities

Biostatistics Resource Group
Bioinformatics Shared Resource

Access to Document

10.1016/j.isci.2022.104551

Cite this

Bondaruk, J., Jaksik, R., Wang, Z., Cogdell, D., Lee, S., Chen, Y., Dinh, K. N., Majewski, T., Zhang, L., Cao, S., Tian, F., Yao, H., Kuś, P., Chen, H., Weinstein, J. N., Navai, N., Dinney, C., Gao, J., Theodorescu, D., ... Czerniak, B. (2022). The origin of bladder cancer from mucosal field effects. iScience, 25(7), Article 104551. https://doi.org/10.1016/j.isci.2022.104551

Bondaruk, J, Jaksik, R, Wang, Z, Cogdell, D, Lee, S, Chen, Y, Dinh, KN, Majewski, T, Zhang, L, Cao, S, Tian, F, Yao, H, Kuś, P, Chen, H , Weinstein, JN , Navai, N , Dinney, C , Gao, J, Theodorescu, D, Logothetis, C , Guo, CC , Wang, W, McConkey, D, Wei, P, Kimmel, M & Czerniak, B 2022, 'The origin of bladder cancer from mucosal field effects', iScience, vol. 25, no. 7, 104551. https://doi.org/10.1016/j.isci.2022.104551

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title = "The origin of bladder cancer from mucosal field effects",

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",

author = "Jolanta Bondaruk and Roman Jaksik and Ziqiao Wang and David Cogdell and Sangkyou Lee and Yujie Chen and Dinh, {Khanh Ngoc} and Tadeusz Majewski and Li Zhang and Shaolong Cao and Feng Tian and Hui Yao and Pawe{\l} Ku{\'s} and Huiqin Chen and Weinstein, {John N.} and Neema Navai and Colin Dinney and Jianjun Gao and Dan Theodorescu and Christopher Logothetis and Guo, {Charles C.} and Wenyi Wang and David McConkey and Peng Wei and Marek Kimmel and Bogdan Czerniak",

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AU - Bondaruk, Jolanta

AU - Jaksik, Roman

AU - Wang, Ziqiao

AU - Cogdell, David

AU - Lee, Sangkyou

AU - Chen, Yujie

AU - Dinh, Khanh Ngoc

AU - Majewski, Tadeusz

AU - Zhang, Li

AU - Cao, Shaolong

AU - Tian, Feng

AU - Yao, Hui

AU - Kuś, Paweł

AU - Chen, Huiqin

AU - Weinstein, John N.

AU - Navai, Neema

AU - Dinney, Colin

AU - Gao, Jianjun

AU - Theodorescu, Dan

AU - Logothetis, Christopher

AU - Guo, Charles C.

AU - Wang, Wenyi

AU - McConkey, David

AU - Wei, Peng

AU - Kimmel, Marek

AU - Czerniak, Bogdan

PY - 2022/7/15

Y1 - 2022/7/15

N2 - 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.

AB - 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.

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The origin of bladder cancer from mucosal field effects

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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