Wu Pu-Yuan, Fan Yi-Mei, Wang Ya-Ping
Department of Medical Genetics,Medical School, Nanjing University,Nanjing, Jiangsu 210093, P. R. China.
Ai Zheng. 2009 Dec;28(12):1236-42. doi: 10.5732/cjc.009.10266.
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.
表观突变是表观遗传调控正常过程中的错误，可导致正常活跃基因的异常转录沉默或正常沉默基因的重新激活。表观突变通常被认为是体细胞事件，局限于受影响的组织。然而，最近对遗传性非息肉病性结直肠癌（HNPCC）患者的研究表明，肿瘤病因之一的MLH1基因启动子区域CpG岛的等位基因特异性高甲基化存在于所有检测的组织中。此外，还报道了其他肿瘤抑制基因（TSG）如MSH2和BRCA1的种系表观突变，这表明表观突变可能发生在种系中（在配子发生或早期胚胎发育期间）。种系表观突变在人类疾病中的作用可能与种系突变同样重要。我们综述了肿瘤抑制基因种系表观突变的最新进展，包括种系表观突变的潜在机制、跨代遗传的可能性及其对我们理解人类疾病的影响。
