[Genetic and epigenetic changes in colorectal cancer and genetic testing for personalized medicine]

Recent studies have uncovered molecular pathways of colorectal cancer, including the chromosomal instability pathway and microsatellite pathway. In addition, according to genetic and epigenetic profiles, colorectal cancer can be subclassified into 3 distinct groups, named the CpG island methylator phenotype (CIMP) 1, CIMP2, and CIMP negative. CIMP1 is characterized by MSI and BRAF mutations and rare KRAS and p53 mutations. CIMP2 is associated with KRAS mutations and rare MSI, BRAF, or p53 mutations. CIMP negative cases have a high rate of p53 mutations and lower rates of MSI or mutations of BRAF or KRAS. Regarding genetic testing for personalized medicine for colorectal cancer, uridine disphosphate glucuronosyl transferase 1(UGT1) and KRAS tests are available. Irinotecan is one of the most effective chemotherapeutic agents in the treatment of metastatic colorectal cancer. The prodrug irinotecan is biotransformed by carboxylesterase into its active metabolite SN-38, which is inactivated by UGT1 into the inactive compound SN-38G. Here we discuss UGT1A1 gene polymorphism as a predictor of toxicity. The epidermal growth factor (EGFR) plays an important role in the development and progression of colorectal cancer. KRAS serves as a mediator between extracellular ligand binding and intracellular transduction of signals from EGFR to the nucleus. Activating KRAS mutations has been identified as a predictor of resistance to EGFR-directed antibodies such as cetuximab. Here we discuss the current understanding of KRAS mutations and the therapeutic effect of cetuximab.