Defective DNA mismatch repair (MMR) occurs in the majority of tumors from patients with hereditary non-polyposis colorectal cancer (HNPCC) and approx 15% of sporadic colorectal cancer (CRC) (1 ,2 ). In HNPCC-associated tumors, defective MMR is most often due to inactivating mutations of the DNA MMR geneshMLH1andhMSH2(3 ,4 ). Defective MMR in sporadic CRC, on the other hand, is generally due to hypermethylation of thehMLH1promoter (5 -7 ). As might be expected, inactivating mutations ofhMSH2andhMLH1lead to a loss ofhMSH2orhMLH1expression respectively and hypermethylation of thehMLH1promoter to a loss ofhMLH1expression (5 -8 ). One of the hallmarks of defective DNA MMR is a type of genetic instability known as microsatellite instability (MSI). Tumors with defective DNA MMR generally exhibit MSI at the majority of the loci examined (MSI-H phenotype) (8 ,9 ).
