Developmental origins of Cancer

Division Of Basic Sciences - Nci

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Abstract

Enhancers and genes were grouped into categories based on their patterns of activation throughout the three stages: fetal, adult, and cancer. The groups of interest are those which are turned off after development, but become reactivated in cancer, and those that turn on only in adult tissues, but turn off again in cancer. We found that these genes which are re-activated and re-repressed are enriched in number compared to the background expectation across three tissue types (lung, colon, and kidney). An additional interesting finding is that enhancers within each of the four expression groups tend to be more linearly clustered in the genome, signifying possible coordinated expression. We are now starting to work with temporal developmental data in multiple tissues to map the cancer-associated expression and splicing changes to specific developmental stages.