An integrated view of colon cancer transcriptional programs provides novel insight into neoplasia

Murine colon tumor adenomas and human CRCs both show adoption and dysregulation of signatures tightly controlled during embryonic mouse colon development. The use of etiologically distinct mouse models of colon cancer allows for the identification of models that resemble different stages of embryonic mouse colon development and that are recapitulated by specific tumor types. All tumors exhibit large-scale activation of developmental patterns. Nuclear β-catenin-positive (and AOM) tumors map more strongly to early development stages during (more proliferative, less differentiated), whereas nuclear β-catenin-negative (and ) tumors map more strongly to later stages consistent with increased epithelial differentiation. Overall representation of the relationship of mouse colon tumor models and human CRC to development and non-developmental expression patterns. Gene expression clusters mapped to the progression of adenomatous and carcinomatous transformation identified in Figures 5 and 6 are shown as the clusters of genes whose expression is either gained or lost associated with the stage of progression. For example normal development could be considered as 'subverted' if there is an absence of expression of genes normally expressed at high level in the developing colon that fail to be expressed in tumors (for example, C18, C19), or that are activated in tumor but not normally expressed in development (C20). Upregulated clusters are enriched for genes with known oncogenic functions and down-regulated clusters for genes associated with tumor suppression. Both mouse colon tumor models and human CRC share in the activation of embryonic colon expression (C22), or partially overlap (C23, dotted lines) the loss or repression of adult differentiation-associated genes (C19), and the loss of tumor suppressor genes (C18). Many human CRCs also lack the expression of additional tumor suppressor programs and gain the expression of oncogenes that are not over-expressed during normal developmental morphogenesis (C21).<p><b>Copyright information:</b></p><p>Taken from "Transcriptional recapitulation and subversion of embryonic colon development by mouse colon tumor models and human colon cancer"</p><p>http://genomebiology.com/2007/8/7/R131</p><p>Genome Biology 2007;8(7):R131-R131.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC2323222.</p><p>