Promoter methylation status of DAP-kinase and RUNX3 genes in neoplastic and non-neoplastic gastric epithelia
Promoter methylation status of DAP-kinase and RUNX3 genes in neoplastic and non-neoplastic gastric epithelia
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DOI：
10.1111/j.1349-7006.2003.tb01447.x
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发表时间：
2003-04-01
期刊：
影响因子：
5.7
通讯作者：
Motoyama, T
中科院分区：
文献类型：
--
作者：
Waki, T;Tamura, G;Motoyama, T
在包括胃癌在内的人类肿瘤中，经常发现由启动子CpG岛的高甲基化引起的肿瘤抑制基因和肿瘤相关基因的沉默。启动子甲基化并不局限于癌细胞，也存在于非肿瘤细胞中作为年龄相关的组织特异性现象。为了阐明胃上皮中DAP激酶和RUNX 3年龄相关甲基化的生理后果，我们研究了这些基因在尸检和手术中获得的肿瘤和非肿瘤胃上皮以及10种胃癌细胞系中的启动子甲基化状态。分别在10%（1/10）和70%（7/10）的细胞系中检测到DAP激酶和RUNX 3甲基化，并且与其表达状态几乎一致。在尸检样本中，这些基因的甲基化在22岁及以下人群的非肿瘤性胃上皮中未见（0%; 0/4）。DAP-激酶在45岁或以上人群的87%（13/15）的非肿瘤性胃上皮细胞中甲基化，而非肿瘤性胃上皮细胞中的RUNX 3甲基化仅限于77岁或以上的个体。在从胃癌患者获得的样本中，在肿瘤性和相应的非肿瘤性胃上皮中均观察到甲基化; DAP激酶的甲基化率分别为43%（40/93）和73%（68/93），RUNX 3的甲基化率分别为45%（42/93）和8%（7/93）。DAP激酶和RUNX 3甲基化的频率在非肿瘤性胃上皮中差异显著（P
Silencing of tumor suppressor and tumor-related genes by hypermethylation at promoter CpG islands is frequently found in human tumors, including gastric cancer. Promoter methylation is not restricted to cancer cells, and is also present in non-neoplastic cells as an age-related tissue-specific phenomenon. To clarify the physiological consequence of DAP-kinase and RUNX3 age-related methylation in gastric epithelia, we investigated the promoter methylation status of these genes in both neoplastic and nonneoplastic gastric epithelia obtained at autopsy and surgery, as well as in 10 gastric cancer cell lines. Methylation of DAP-kinase and RUNX3 was detected in 10% (1/10) and 70% (7/10) of the cell lines, respectively, and was almost concordant with their expression status. Among autopsy samples, methylation of these genes was not seen in non-neoplastic gastric epithelia from persons who were aged 22 years and below (0%; 0/4). DAP-kinase was methylated in 87% (13/15) of non-neoplastic gastric epithelia of persons who were aged 45 years or older, while RUNX3 methylation in non-neoplastic gastric epithelia was restricted to individuals who were aged 77 years or older. Among samples obtained from patients with stomach cancer, methylation was observed in both the neoplastic and the corresponding nonneoplastic gastric epithelia; 43% (40/93) and 73% (68/93) for DAP-kinase, and 45% (42/93) and 8% (7/93) for RUNX3, respectively. Frequencies of DAP-kinase and RUNX3 methylation differed significantly in non-neoplastic gastric epithelia (P