The origin of bladder cancer from mucosal field effects

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.

Automated summary

Whole-organ mapping identified dysregulated pathways and immune response involvement in bladder cancer development. Aberrant methylation/expression of genes and different types of mutations were found to be associated with disease progression. The carcinogenesis process can be divided into dormant and progressive phases.