Hereditary nonpolyposis colorectal cancer and lynch syndrome

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant cancer disorder associated with a greatly increased risk of colorectal, uterine, and other cancers. Most cases of HNPCC are due to inherited mutations in DNA mismatch repair (MMR) genes and their encoded proteins which correct errors made during DNA replication. HNPCC associated with inherited MMR defects is also called Lynch syndrome. Additionally, sporadic cancers occurring in individuals without HNPCC may have diminished expression of MMR protein(s) due to epigenetic silencing. Defective MMR function leads to reduced fidelity of DNA synthesis and microsatellite instability (MSI), the accumulation of mutations in repetitive sequences of DNA called microsatellites. Testing for defective MMR can be done directly by immunohistochemical staining for MMR proteins or indirectly by PCR fragment analysis of microsatellites.