Departments of Surgical Oncology & Pathology, W350, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Epigenomics. 2011 Feb;3(1):19-34. doi: 10.2217/epi.10.64.
This article focuses on the epigenetic alterations of aberrant promoter hypermethylation of genes, and histone modifications or RNA interference in cancer cells. Current knowledge of the hypermethylation of allele(s) in classical tumor suppressor genes in inherited and sporadic cancer, candidate tumor suppressor and other cancer genes is summarized gene by gene. Global and array-based studies of tumor cell hypermethylation are discussed. The importance of standardization of scoring of the methylation status of a gene is highlighted. The histone marks associated with hypermethylated genes, and the miRNAs with dysregulated expression, in kidney or bladder tumor cells are also discussed. Kidney cancer has the highest mortality rate of the genito-urinary cancers. There are management issues associated with the high recurrence rate of superficial bladder cancer, while muscle-invasive bladder cancer has a poor prognosis. These clinical problems are the basis for the translational application of gene hypermethylation in the diagnosis and prognosis of kidney and bladder cancer.
本文重点介绍了癌症细胞中基因启动子异常高甲基化、组蛋白修饰或 RNA 干扰的表观遗传改变。本文按基因逐个总结了经典肿瘤抑制基因的等位基因在遗传性和散发性癌症、候选肿瘤抑制基因和其他癌症基因中异常高甲基化的最新知识。讨论了基于全基因组和阵列的肿瘤细胞高甲基化研究。强调了基因甲基化状态评分标准化的重要性。还讨论了与肾或膀胱肿瘤细胞中高甲基化基因相关的组蛋白标记物和表达失调的 miRNAs。肾细胞癌是泌尿生殖系统癌症中死亡率最高的癌症。与浅表膀胱癌高复发率相关的有治疗管理问题,而肌层浸润性膀胱癌预后不良。这些临床问题是基因高甲基化在肾和膀胱癌诊断和预后中的转化应用的基础。