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Role of DNA Mismatch Repair Defects in the Pathogenesis of Human Cancer

Päivi Peltomäki

From the Department of Medical Genetics, University of Helsinki, Finland; and Division of Human Cancer Genetics, The Ohio State University, Columbus, OH.

Address reprint requests to Päivi Peltomäki, MD, Department of Medical Genetics, Biomedicum Helsinki, P.O. Box 63 (Haartmaninkatu 8), FIN-00014 University of Helsinki, Finland; email: paivi.peltomaki{at}helsinki.fi.

The DNA mismatch repair (MMR) system is necessary for the maintenance of genomic stability. In a broad sense, all main functions of the MMR system, including the correction of biosynthetic errors, DNA damage surveillance, and prevention of recombination between nonidentical sequences serve this important purpose. Failure to accomplish these functions may lead to cancer. It is therefore not surprising that inherited defects in the MMR system underlie one of the most prevalent cancer syndromes in humans, hereditary nonpolyposis colon cancer (HNPCC). In addition, acquired defects of the same system may account for 15% to 25%, or even a higher percentage, of sporadic cancers of different organs of the "HNPCC spectrum," including the colon and rectum, uterine endometrium, stomach, and ovaries. Recent studies indicate that the MMR genes may be involved in the pathogenesis of even a broader spectrum of tumors in one way or another. An updated review of the different features of the human MMR system will be provided, with the emphasis on their implications in cancer development.

Supported by grants from the Sigrid Juselius Foundation, Academy of Finland, Finnish Cancer Foundation, and the National Institutes of Health (CA82282).

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