Raval Aparna, Byrd John C, Plass Christoph
Department of Molecular Virology, Immunology, and Medical Genetics, Division of Human Cancer Genetics, The Ohio State University, Columbus, OH 43210, USA.
Semin Oncol. 2006 Apr;33(2):157-66. doi: 10.1053/j.seminoncol.2005.12.011.
Enormous evidence has accumulated in the past decades that establishes the importance of epigenetic modifications in cancer and has resulted in shifting the focus from entirely genetic-based studies to integrated studies involving both genetic and epigenetic alterations. Chronic lymphocytic leukemia (CLL) is one such example where studies involving epigenetic aberrations have accelerated the search for affected genes, which was initially restricted to commonly deleted chromosomal regions. Many novel genes that are epigenetically silenced in CLL have been identified. Advances in the understanding of post-translational histone modifications and DNA methylation in normal and in CLL cells have proven to be extremely beneficial in finding powerful diagnostic markers, as well as in exploring novel therapies. At present, the field of epigenetics is at an evolving stage, but there is no doubt that further unraveling of its cause and effects in transformed cells will bring a new revolution in cancer therapeutics.
在过去几十年里,大量证据表明表观遗传修饰在癌症中具有重要性,这使得研究重点从完全基于基因的研究转向涉及基因和表观遗传改变的综合研究。慢性淋巴细胞白血病(CLL)就是这样一个例子,涉及表观遗传异常的研究加速了对受影响基因的寻找,最初这一寻找仅限于常见的染色体缺失区域。许多在CLL中表观遗传沉默的新基因已被鉴定出来。对正常细胞和CLL细胞中翻译后组蛋白修饰和DNA甲基化的理解进展,已被证明在寻找强大的诊断标志物以及探索新疗法方面极为有益。目前,表观遗传学领域正处于发展阶段,但毫无疑问,进一步揭示其在转化细胞中的因果关系将给癌症治疗带来一场新的革命。