Spreading of methylation within RUNX3 CpG island in gastric cancer
Spreading of methylation within RUNX3 CpG island in gastric cancer
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DOI：
10.1111/j.1349-7006.2005.00133.x
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发表时间：
2006-01-01
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：
Homma, N;Tamura, G;Motoyama, T
RUNX 3是一个新的肿瘤抑制基因，在胃癌中经常被启动子高甲基化沉默。在胃癌细胞系、原发性胃癌和非肿瘤性胃粘膜中检查了RUNX 3启动子CpG岛（3478 bp）内多个区域的甲基化状态，以阐明甲基化如何在CpG岛内扩散。通过分析细胞系评价RUNX 3沉默的关键区域。90%（9/10）的胃癌细胞株、96%（43/45）的原发性胃癌和96%（43/45）的非肿瘤性胃粘膜中CpG岛最5'端甲基化。在转录起始位点附近的甲基化频率较低，在细胞系中为40%（4/10），在原发性胃癌中为53%（24/45），在非肿瘤性胃粘膜中为11%（5/45），其中甲基化被证明是基因沉默的关键。因此，超甲基化最初发生在RUNX 3 CpG岛的最5'区域，并在最终关闭RUNX 3 mRNA表达之前扩散到转录起始位点。检测RUNX 3 CpG岛多个区域的甲基化可能有助于胃癌的诊断和风险评估。
RUNX3 is a novel tumor suppressor gene that is frequently silenced by promoter hypermethylation in gastric cancer. The methylation status of multiple regions within the RUNX3 promoter CpG island (3478 bp) was examined in gastric cancer cell lines, primary gastric cancers and non-neoplastic gastric mucosa to clarify how methylation spreads within the CpG island. The critical regions for RUNX3 silencing were evaluated by analysis of cell lines. The most 5' region of the CpG island was methylated in 90% (9/10) of gastric cancer cell lines, 96% (43/45) of primary gastric cancers and in 96% (43/45) of non-neoplastic gastric mucosa. The frequencies of methylation were less near the transcription start site and were 40% (4/10) in cell lines, 53% (24/45) in primary gastric cancers and 11% (5/45) in non-neoplastic gastric mucosa, where methylation was proven to be critical for gene silencing. Thus, hypermethylation initially occurs at the most 5' region of the RUNX3 CpG island and spreads to the transcription start site before ultimately shutting down RUNX3 mRNA expression. The detection of hypermethylation at multiple regions within the RUNX3 CpG island may be useful in the diagnosis and risk assessment of gastric cancer.