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《Chinese Journal of Cancer》 2009-12
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Germ-line epimutations and human cancer

Pu-Yuan Wu,1,2 Yi-Mei Fan1,2 and Ya-Ping Wang1,2 1. Department of Medical Genetics, Medical School, Nanjing University, Nanjing, Jiangsu 210093, P. R. China 2. Jiangsu Key Laboratory of Molecular Medicine, Nanjing, Jiangsu 210093, P. R. China  
Epimutations are errors in the normal process of epigenetic regulation which can result in aberrant transcriptional silencing of a normally active gene or reactivation of a normally silent gene. Epimutations are generally considered to be somatic events and to be confined in affected tissues. However, recent studies of patients with hereditary nonpolyposis colorectal cancer (HNPCC) have showed that allele-specific hypermethylation of CpG islands in the promoter region of the MLH1 gene, one of the causes of the tumor, existed in all the tissues examined. In addition, germ-line epimutations of other tumor suppressor genes (TSGs), such as MSH2 and BRCA1, have also been reported, demonstrating that epimutations might arise in the germ- line (during gametogenesis or early embryonic development). The role of germ-line epimutations might be as important as germ-line mutations in human disease. We reviewed the update on germ-line epimutations of TSGs including the possible mechanisms underlying germ-line epimutations, the possibility of transgenerational inheritance, and their impact on our understanding of human disease.
【Fund】: 江苏省自然科学基金项目(编号:BK2008269);; 江苏省国际科技合作计划项目(编号:BZ2008055)~~
【CateGory Index】: R730.2
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