Department of Pathology, The Fourth Hospital Affiliated to Soochow University, 200 Huihe Road, Wuxi, 214062, Jiangsu, China.
Med Oncol. 2011 Dec;28(4):1218-24. doi: 10.1007/s12032-010-9651-8. Epub 2010 Aug 17.
Methylation in the promoter region is one of the mechanisms through which tumor suppressors are inactivated, resulting in tumorigenesis and/or tumor progression. Herein, we studied the methylation status in the promoter region of the p14ARF tumor suppressor gene in 33 brain tissues isolated from glioma patients (astrocytomas) and compared to 12 brain tissues isolated from autopsy donors using methylation-specific polymerase chain reaction (MSP). The correlation between the expression of P14 and P53 was investigated using immunohistochemistry (IHC). The average percentage of methylation in the promoter region of p14ARF gene in brain samples from glioma patients is 39.4%, while 0 from autopsy donors. No difference in the methylation level between low-grade and high-grade gliomas was detected. The methylation status has no correlation with the prognosis in glioma patients. A significant correlation between the expression of mutant form of TP53 and the grade of the glioma was established. Furthermore, there was a negative correlation between methylation of the p14ARF promoter and the expression of the mutant form of TP53. Therefore, our data suggest that methylation in the promoter region of the p14ARF gene may be used as a biomarker for the diagnosis of gliomas.
甲基化是肿瘤抑制基因失活的机制之一,导致肿瘤发生和/或肿瘤进展。在此,我们通过甲基化特异性聚合酶链反应(MSP)研究了 33 例脑胶质瘤患者脑组织和 12 例尸检供体组织中 p14ARF 肿瘤抑制基因启动子区的甲基化状态。采用免疫组织化学(IHC)研究 P14 和 P53 的表达相关性。脑胶质瘤患者组织中 p14ARF 基因启动子区的甲基化平均百分比为 39.4%,而尸检供体组织中无甲基化。低级别和高级别胶质瘤之间的甲基化水平无差异。甲基化状态与胶质瘤患者的预后无关。突变型 TP53 的表达与胶质瘤的分级有显著相关性。此外,p14ARF 启动子的甲基化与突变型 TP53 的表达呈负相关。因此,我们的数据表明,p14ARF 基因启动子区的甲基化可作为胶质瘤诊断的生物标志物。