Genetic instability and methylation tolerance in colon cancer.

Microsatellite instability was first identified in colon cancer and later shown to be due to mutations in genes responsible for correction of DNA mismatches. Several human mismatch correction genes that are homologous to those of yeast and bacteria have been identified and are mutated in families affected by the hereditary non-polyposis colorectal carcinoma (HNPCC) syndrome. Similar alterations have been also found in some sporadic colorectal cancers. The mismatch repair pathway corrects DNA replication errors and repair-defective colorectal carcinoma cell lines exhibit a generalized mutator phenotype. An additional consequence of mismatch repair defects is cellular resistance, or tolerance, to certain DNA damaging agents.