Genomic Instability and Epigenetic Alteration in Colorectal Carcinogenesis

Colorectal cancer results from the progressive accumulation of genetic and epigenetic alterations that lead to cellular transformation and tumor progression, which is known as the adenoma-carcinoma sequence. Genomic instability, including chromosomal instability and microsatellite instability, creates a permissive state in which a cell acquires enough mutations to be transformed to a cancer cell. Epigenetic alteration is a more recently appreciated heritable alteration that has been found to occur commonly in colorectal cancer. Epigenetic alterations are clonal changes in gene expression without accompanying changes in primary DNA coding sequences. A subset of colorectal cancer shows cancer-specific promoter hypermethylation of several genes simultaneously, so-called CpG island methylator phenotype (CIMP) positive. The understanding of genetic and epigenetic alterations in colorectal carcinogenesis will yield more effective diagnostic and therapeutic strategies for colorectal cancer.