Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Curr Top Microbiol Immunol. 2012;355:189-216. doi: 10.1007/82_2011_165.
Profound changes in the epigenetic landscape of cancer cells underlie the development of human malignancies. These changes include large-scale DNA methylation changes throughout the genome as well as alterations in the compendium of post-translational chromatin modifications. Epigenetic aberrations impact multiple steps during tumorigenesis, ultimately promoting the selection of neoplastic cells with increasing pathogenicity. Identification of these alterations for use as predictive and prognostic biomarkers has been a highly sought after goal. Recent advances in the field have not only greatly expanded our knowledge of the epigenetic changes driving neoplasia but also demonstrated their significant clinical utility as cancer biomarkers. These biomarkers have proved to be useful for identifying patients whose malignancies are sensitive to specific cytotoxic chemotherapies and may hold promise for predicting which patients will benefit from newer targeted agents directed at oncogenes. The recent application of global analysis strategies has further accelerated our understanding of the epigenome and promises to enhance the identification of epigenomic programs underlying cancer progression and treatment response.
癌症细胞中的表观遗传景观发生深刻变化是人类恶性肿瘤发展的基础。这些变化包括整个基因组中的大规模 DNA 甲基化变化，以及翻译后染色质修饰总集的改变。表观遗传异常影响肿瘤发生过程中的多个步骤，最终促进了具有更高致病性的肿瘤细胞的选择。将这些改变识别为预测和预后生物标志物一直是一个备受关注的目标。该领域的最新进展不仅极大地扩展了我们对驱动肿瘤发生的表观遗传变化的认识，还证明了它们作为癌症生物标志物的重要临床应用价值。这些生物标志物已被证明可用于识别对特定细胞毒性化疗敏感的患者，并且可能有望预测哪些患者将从针对癌基因的新型靶向药物中受益。最近应用的全局分析策略进一步加速了我们对表观基因组的理解，并有望增强对癌症进展和治疗反应背后的表观基因组程序的识别。
