The hMSH2 and hMLH1 genes in hereditary nonpolyposis colorectal cancer.
Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common inherited colorectal cancer predisposing condition. HNPCC is an important problem for the surgeon because up to 60% of carriers of mismatch repair (MMR) gene mutations develop colorectal cancer (CRC), commonly before age 50 years. When CRC is diagnosed, the surgeon is in the ideal position to order appropriate tumor testing for microsatellite instability or immunohistochemical stains for loss of MMR gene associated protein, if this has not already been done. This article reviews the history of HNPCC, its clinical features, gene discovery, development of clinical genetic workup, and clinical surveillance, with an emphasis on the two major HNPCC genes, hMSH2 and hMLH1. It is not always possible to discuss these specific genes without commenting on the broader problem of HNPCC diagnosis and management.
Lynch
Patrick M
PM
Department of Gastrointestinal Medicine and Nutrition, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. plynch@mdanderson.org
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics*; D004260:DNA Repair; D006801:Humans; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein