Genetic and Epigenetic Events Generate Multiple Pathways in
Colorectal Cancer Progression
Figure 1
Genomic instability and multiple pathways in colorectal cancer pathogenesis. (a) Comparison of the numerical chromosomal abnormalities between two representative colon cancer cell lines characterized by CIN (highly rearranged aneuploid karyotype) and MSI (diploid karyotype), respectively. The images are publicly available on the web at: http://www.path.cam.ac.uk. (b) Three distinct parallel pathways with the approximate indicated prevalence are implicated in colon cancer pathogenesis: traditional, alternative, and serrated. The sequential of genetic and epigenetic changes occurring in each pathway are simplified, along with the characteristic precursor lesions (adenomas) and distinctive molecular features of the corresponding carcinomas. The traditional and serrated pathways are more homogeneous and clearly distinguishable; the alternative is more heterogeneous. The best known genetic/epigenetic alterations are indicated in bold, the poorly understood or hypothetical pathways are indicated in italics. APC, adenomatous polyposis coli; MSI, microsatellite instability; CIMP, CpG island methylator phenotype; CIMPL, CIMP-low; CIN, chromosomal instability; MSS, microsatellite stable; BER, base excision repair pathway; Methyl, DNA methylation silencing in yet unknown genes; WNT, wingless pathway; EMT, epithelial mesenchymal transition; TGFβ, transforming growth factor-beta; LOH, loss-of-heterozigosity. Note: tumor microenvironment indicates the crosstalk between cancer cells and cells of the neoplastic stroma.
