采用甲基化特异性 DNA 微阵列对肿瘤和非肿瘤胃上皮中的基因甲基化进行定量评估。

Quantitative assessment of gene methylation in neoplastic and non-neoplastic gastric epithelia using methylation-specific DNA microarray.

机构信息

Department of Pathology and Laboratory Medicine, Yamagata Prefectural Central Hospital, Yamagata, Japan.

出版信息

Pathol Int. 2009 Dec;59(12):895-9. doi: 10.1111/j.1440-1827.2009.02458.x.

DOI:10.1111/j.1440-1827.2009.02458.x

PMID:20021617

Abstract

A fiber-type DNA microarray was used to calculate methylation rates (MR) of four tumor suppressor genes, lysyl oxidase (LOX), p16, RUNX3, and tazarotene-induced gene 1 (TIG1). MR were calculated in 26 primary gastric cancers and corresponding non-neoplastic gastric epithelia, and the results were compared to those of conventional methylation-specific polymerase chain reaction (MSP). MR ranged from 0.1% to 69.1% (mean, 18.3%) for LOX, 0.5-74.1% (mean, 15.7%) for p16, 0.2-76.5% (mean, 22.7%) for RUNX3, and 0.6-41.2% (mean, 5.8%) for TIG1 in primary gastric cancers, and from 0.1% to 25.8% (mean, 8.7%) for LOX, 1.0- 23.2% (mean, 10.3%) for p16, 0.7-25.1% (mean, 5.5%) for RUNX3, and 1.8-27.6% (mean, 11.4%) for TIG1 in corresponding non-neoplastic gastric epithelia. Although MR varied significantly across different samples for both neoplastic and non-neoplastic gastric epithelia, high-level methylation (MR >40%) was cancer specific and was observed in 19.2%, 19.2%, 30.8%, and 3.8% of primary gastric cancers for LOX, p16, RUNX3, and TIG1, respectively. All samples with high-level methylation, as well as some samples with low MR (particularly <10%) were judged to be methylation positive on conventional MSP. Quantitative analysis of gene methylation using methylation-specific DNA microarray is a promising method for cancer diagnosis.

摘要

使用纤维型 DNA 微阵列来计算四个肿瘤抑制基因（赖氨酸氧化酶 [LOX]、p16、RUNX3 和他扎罗汀诱导基因 1 [TIG1]）的甲基化率（MR）。在 26 例原发性胃癌及其相应的非肿瘤性胃上皮中计算了 MR，并将结果与传统的甲基化特异性聚合酶链反应（MSP）进行了比较。原发性胃癌中 LOX 的 MR 范围为 0.1%至 69.1%（平均值为 18.3%），p16 的 MR 范围为 0.5%至 74.1%（平均值为 15.7%），RUNX3 的 MR 范围为 0.2%至 76.5%（平均值为 22.7%），TIG1 的 MR 范围为 0.6%至 41.2%（平均值为 5.8%），而非肿瘤性胃上皮中 LOX 的 MR 范围为 0.1%至 25.8%（平均值为 8.7%），p16 的 MR 范围为 1.0%至 23.2%（平均值为 10.3%），RUNX3 的 MR 范围为 0.7%至 25.1%（平均值为 5.5%），TIG1 的 MR 范围为 1.8%至 27.6%（平均值为 11.4%）。尽管肿瘤和非肿瘤性胃上皮的不同样本之间的 MR 差异显著，但高甲基化（MR>40%）是癌症特异性的，在 LOX、p16、RUNX3 和 TIG1 的原发性胃癌中分别观察到 19.2%、19.2%、30.8%和 3.8%的病例。所有高甲基化水平的样本，以及一些低 MR（特别是 <10%）的样本，在传统 MSP 中被判断为甲基化阳性。使用甲基化特异性 DNA 微阵列进行基因甲基化的定量分析是一种有前途的癌症诊断方法。