Faculty, Staff and Student Publications
Publication Date
7-15-2022
Journal
IScience
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
DOI
10.1016/j.isci.2022.104551
PMID
35747385
PMCID
PMC9209726
PubMedCentral® Posted Date
6-7-2022
PubMedCentral® Full Text Version
Post-print
Correction
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons
Comments
This article has been corrected. See iScience. 2022 Jul 4;25(7):104715.