癌症表观遗传学：人类癌症中的DNA甲基化与染色质改变

Cancer epigenetics: DNA methylation and chromatin alterations in human cancer.

作者信息

Esteller Manel

机构信息

Cancer Epigenetics Laboratory, Spanish National Cancer Center (CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain.

出版信息

Adv Exp Med Biol. 2003;532:39-49. doi: 10.1007/978-1-4615-0081-0_5.

DOI:10.1007/978-1-4615-0081-0_5

PMID:12908548

Abstract

Aberrations in the DNA methylation patterns are nowadays recognized as a hallmark of human cancer. One of the most characteristic changes is the hypermethylation of CpG islands of tumor suppressor genes associated with their transcriptional silencing. The target genes are distributed in all cellular pathways (apoptosis, DNA repair, cell cycle, cell adherence, etc.). They are "classical" tumor suppressor genes with associated familial cancers (BRCA1, hMLH1, p16INK4a, VHL, etc.) and putative new tumor suppressor genes which loss may contribute to the transformed phenotype (MGMT, p14ARF, GSTP1, RARB2, etc.). A tumor-type specific profile of CpG island hypermethylation exist in human cancer that allows the use of these aberrantly hypermethylated loci as biomarkers of the malignant disease. The eruption of new technologies for the careful study of the DNA methylation patterns, and their genetic partners in accomplishing gene silencing, it may also provide us with new drugs for the epigenetic treatment of human tumors.

摘要

如今，DNA甲基化模式的异常被认为是人类癌症的一个标志。最典型的变化之一是与转录沉默相关的肿瘤抑制基因的CpG岛发生高甲基化。这些靶基因分布于所有细胞途径（细胞凋亡、DNA修复、细胞周期、细胞黏附等）中。它们包括具有相关家族性癌症的“经典”肿瘤抑制基因（BRCA1、hMLH1、p16INK4a、VHL等）以及其缺失可能导致转化表型的假定新肿瘤抑制基因（MGMT、p14ARF、GSTP1、RARB2等）。人类癌症中存在CpG岛高甲基化的肿瘤类型特异性谱，这使得这些异常高甲基化位点可作为恶性疾病的生物标志物。随着用于仔细研究DNA甲基化模式及其在实现基因沉默中的遗传伙伴的新技术的出现，这也可能为我们提供用于人类肿瘤表观遗传治疗的新药物。