Molecular evolution of colorectal cancer: from multistep carcinogenesis to the big bang

摘要: Colorectal cancer is characterized by exquisite genomic instability either in the form of microsatellite or chromosomal instability. Microsatellite result mutation mismatch repair genes their silencing through promoter methylation as a consequence CpG island methylator phenotype. The molecular causes are less well characterized. Genomic and field cancerization lead to high degree intratumoral heterogeneity determine formation stem cells epithelial-mesenchymal transition mediated TGF-β APC pathways. Recent analyses using integrated genomics reveal different phases colorectal evolution. An initial phase that yields many clones with mutations (big bang) followed an important, previously not detected evolution consists stabilization several relatively flat outgrowth. big bang model can best explain coexistence stable compatible fact analysis bulk primary tumor prognostic information.