Mouse colon development series

Goal of the experiment: To identify transcriptional patterns across tumors from colorectal cancer murine models and normal mouse colon samples at different developmental stages. Experiment description: Colorectal cancer (CRC) results from multiple genetic and epigenetic events that produce variable histologies and clinical outcomes. To identify gene regulatory programs that underlie colon tumorigenesis, we profiled gene expression in 39 mouse colon tumors from four independent mouse models and compared this to mouse colon embryonic development, as well as with 100 human colon carcinomas. Here, we report a striking recapitulation of embryonic patterns of gene expression in both mouse and human colon tumors. All four of the mouse colon tumor models exhibited large-scale activation of embryonic gene expression signatures. The two nuclear beta-catenin-positive mouse tumors (azoxymethane-treated [AOM] and ApcMin/+), exhibited strong activation of genes characteristic of those expressed in the earliest embryonic stages, while tumors from two other models (Smad3-/- and Tgfb1-/- x Rag2-/-) exhibited lower activation of early stage-specific genes but substantial expression of general embryonic colon genes. Human colon cancer cases over-expressed genes characteristic of both early and late embryonic stages. Examining tumor gene expression through the lens of development has revealed an extensive network of therapeutic targets for cancer control. Keywords: Tumors from four murine models of colorectal cancer and normal mouse colon samples at different developmental stages Four colorectal tumor models were compared using the approach of finding model-specific differences with gene expression levels referenced to the median gene expression value across all models. A second complementary strategy compared the gene expression levels of the murine tumors to those of mouse normal adult colon.