HEREDITARY NONPOLYPOSIS COLORECTAL CANCER

HNPCC

(215)955-1011

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) is a hereditary cancer predisposition syndrome predominantly presenting with colorectal cancer. One cause is an alteration in one or more of the mismatch repair genes. These genes are responsible for the detection and repair of DNA mutations occurring during DNA replication. The majority of inherited genetic alterations in HNPCC occur in the hMSH2 and hMLH1 genes however, mutations in other genes, e.g., hPMS2 or hMSH6, have also been described. Normally two copies of each gene are inherited: one from each parent. Cancer occurs when one inherits a defective gene from one of the parents and during the life of the individual, the second gene is altered in a cell that then develops into a cancer. A hallmark of HNPCC tumors that are a result of altered mismatch repair genes is instability of simple repeat DNA sequences (termed: microsatellite instability). Also, in greater than 90% of these tumors, one can observe loss of mismatch repair protein expression. These two indicators, microsatellite instability and loss-of-protein expression, form the basis of the HNPCC screening test. Once the HNPCC screening test is performed and the results appear to indicate the involvement of mismatch repair genes, then a direct DNA sequencing for alteration of the genes can be carried-out.