DNA methylation profiles in precancerous tissue and cancers: carcinogenetic risk estimation and prognostication based on DNA methylation status
DNA methylation profiles in precancerous tissue and cancers: carcinogenetic risk estimation and prognostication based on DNA methylation status
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DOI：
10.2217/epi.10.16
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发表时间：
2010-06-01
期刊：
影响因子：
3.8
通讯作者：
Kanai, Yae
中科院分区：
文献类型：
--
作者：
Arai, Eri;Kanai, Yae
DNA甲基化的改变与DNA甲基转移酶异常相关，并导致肿瘤相关基因沉默和染色体不稳定，甚至涉及各种器官的癌前病变。DNA甲基化改变也是人类癌症的组织学异质性和临床病理学多样性的原因。因此，我们分析了临床组织样本中全基因组范围内的DNA甲基化。我们使用基于细菌人工染色体阵列的甲基化CpG岛扩增方法的方法揭示了与未来更多恶性癌症发展相关的DNA甲基化改变已经在肾脏，肝脏和泌尿道的癌前阶段积累。癌前阶段的DNA甲基化谱基本上由个体患者中发展的相应癌症遗传。这样的DNA甲基化改变可能赋予进一步的遗传和表观遗传改变的脆弱性，产生更多的恶性癌症，从而决定患者的结果。基于细菌人工染色体阵列的甲基化CpG岛扩增数据的基础上，已经建立了致癌风险评估的指标，使用来自肝炎病毒感染、慢性肝炎和肝硬化或组织学正常的尿路上皮患者的肝组织标本，以及使用来自肾细胞癌、肝细胞癌和尿路上皮癌患者的活检或手术切除标本进行鉴定。这样的全基因组DNA甲基化谱现在已经牢固地建立了翻译表观遗传学的临床相关性。
Alterations in DNA methylation, which are associated with DNA methyltransferase abnormalities and result in silencing of tumor-related genes and chromosomal instability, are involved even in precancerous changes in various organs. DNA methylation alterations also account for the histological heterogeneity and clinicopathological diversity of human cancers. Therefore, we have analyzed DNA methylation on a genome-wide scale in clinical tissue samples. Our approach using the bacterial artificial chromosome array-based methylated CpG island amplification method has revealed that DNA methylation alterations correlated with the future development of more malignant cancers are already accumulated at the precancerous stage in the kidney, liver and urinary tract. DNA methylation profiles at precancerous stages are basically inherited by the corresponding cancers developing in individual patients. Such DNA methylation alterations may confer vulnerability to further genetic and epigenetic alterations, generate more malignant cancers, and thus determine patient outcome. On the basis of bacterial artificial chromosome array-based methylated CpG island amplification data, indicators for carcinogenetic risk estimation have been established using liver tissue specimens from patients with hepatitis virus infection, chronic hepatitis and liver cirrhosis or histologically normal urothelia, and for prognostication using biopsy or surgically resected specimens from patients with renal cell carcinoma, hepatocellular carcinoma and urothelial carcinoma. Such genome-wide DNA methylation profiling has now firmly established the clinical relevance of translational epigenetics.