Screening for Lynch Syndrome by Microsatellite Instability Analysis

Hereditary nonpolyposis colorectal cancer (HNPCC) is an inherited cancer syndrome characterized by early onset colorectal cancer as well as endometrial, urinary tract, small bowel, ovarian, gastric, pancreatic, hepatobiliary, brain, and skin tumors. HNPCC is an autosomal dominant syndrome defined by family history and clinical criteria1, and it accounts for approximately 2 % of all colorectal cancers. In a subset of HNPCC patients, as well as in some colorectal cancer patients that do not meet the formal criteria for HNPCC, the cancer predisposition is caused by germline mutations in DNA mismatch repair (MMR) genes. The identification of inherited MMR mutations by genetic testing impacts the care and surveillance of the patient2 and enables predictive testing of family members. Individuals with germline mutations in one of the MMR genes are defined as having Lynch syndrome. The revised Bethesda Guidelines3 established criteria to identify individuals at increased risk for Lynch syndrome based on clinical information, family history, or histology; however, most individuals identified by the revised guidelines do not have Lynch syndrome. Furthermore, geneti