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Familial Cancer

, Volume 4, Issue 3, pp 227–232 | Cite as

Lynch Syndrome Genes

  • Päivi PeltomäkiEmail author
Article

Abstract

Since the discovery of the major human genes with DNA mismatch repair (MMR) function in 1993--1995, mutations in four, MSH2, MLH1, MSH6, and PMS2, have been convincingly linked to susceptibility of hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome. Among these, PMS2 mutations are associated with diverse clinical features, including those of the Turcot syndrome. Two additional MMR genes, MLH3 and PMS1, have also been proposed to play a role in Lynch syndrome predisposition, but the clinical significance of mutations in these genes is less clear. According to the database maintained by the International Collaborative Group on Hereditary Nonpolyposis Colorectal Cancer (ICG-HNPCC), current InSiGHT (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different HNPCC-associated MMR gene mutations are known that primarily involve MLH1 (~50%), MSH2 (~40%), and MSH6 (~10%). Examination of HNPCC/Lynch syndrome-associated MMR genes and their mutations has revealed several other important functions for their protein products beyond postreplicative mismatch repair as well as many alternative mechanisms of pathogenicity. Despite these advances, much is yet to be learned about the molecular basis of correlations between genetic changes and clinical features of the disease.

Keywords

hereditary nonpolyposis colorectal cancer MLH1 MLH3 MSH2 MSH6 PMS2 

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Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Department of Medical Genetics, Biomedicum HelsinkiUniversity of HelsinkiFinland

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