Age-related methylation of tumor suppressor and tumor-related genes: an analysis of autopsy samples
Age-related methylation of tumor suppressor and tumor-related genes: an analysis of autopsy samples
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DOI：
10.1038/sj.onc.1206651
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发表时间：
2003-06-26
期刊：
影响因子：
8
通讯作者：
Motoyama, T
中科院分区：
文献类型：
--
作者：
Waki, T;Tamura, G;Motoyama, T
与年龄相关的甲基化可能表现为一个突变过程。为了阐明肿瘤抑制基因和肿瘤相关基因的年龄相关甲基化的生理后果，我们研究了通过甲基化特异性PCR在尸检中获得的各种器官非肿瘤细胞中的启动子甲基化状态。我们研究了在人类某些恶性肿瘤中经常沉默的APC、dap -激酶、E-cadherin、GSTP1、hMLH1、p16、RASSF1A和RUNX3基因的启动子甲基化状态，这些基因在38例日本尸体解剖的食管、胃、小肠和大肠、肝脏、胰腺、肾脏和肺的非肿瘤细胞中被甲基化。除APC和RASSF1A外，肿瘤抑制基因和肿瘤相关基因在32岁以下人群的样本中通常未甲基化（n = 11）。在42岁以上人群（n = 27）的样本中，甲基化启动子以不同频率以组织特异性的方式存在，尽管GSTP1和hMLH1甲基化不存在或很少发生，并且缺乏组织特异性。在大多数器官中，与年龄相关的甲基化发生率与恶性器官中报道的甲基化发生率相似。因此，与年龄相关的一组不同基因的甲基化被认为构成了不同器官的场缺陷。
Age-related methylation may have the potential to behave as a mutator process. To clarify the physiological consequence of age-related methylation of tumor suppressor and tumor-related genes, we studied promoter methylation status in non-neoplastic cells of various organs obtained at autopsy by methylation-specific PCR. Promoter methylation status of APC, DAP-kinase, E-cadherin, GSTP1, hMLH1, p16, RASSF1A and RUNX3 genes, which are frequently silenced in certain human malignancies, was studied in non-neoplastic cells of the esophagus, stomach, small and large intestines, liver, pancreas, kidney and lung obtained from 38 Japanese autopsies. The tumor suppressor and tumor-related genes, except APC and RASSF1A, were generally unmethylated in samples obtained from people who were less than 32 years old (n = 11). Methylated promoters were present at variable frequencies in a tissue-specific manner in samples obtained from people who were greater than 42 years old (n = 27), although GSTP1 and hMLH1 methylation was absent or infrequent and lacked tissue specificity. In the majority of organs, the incidence of age-related methylation paralleled the reported methylation incidence in malignant counterparts. Thus, age-related methylation of a different set of genes is thought to constitute a field defect in different organs.