Kuo Lu-Ting, Lu Hsueh-Yi, Lee Chien-Chang, Tsai Jui-Chang, Lai Hong-Shiee, Tseng Ham-Min, Kuo Meng-Fai, Tu Yong-Kwang
Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan.
Department of Industrial Engineering and Management, National Yunlin University of Science and Technology, Douliu, Yunlin county, 640, Taiwan.
Cancer Med. 2016 Aug;5(8):1830-9. doi: 10.1002/cam4.762. Epub 2016 Jul 1.
Aberrant methylation has been associated with transcriptional inactivation of tumor-related genes in a wide spectrum of human neoplasms. The influence of DNA methylation in oligodendroglial tumors is not fully understood. Genomic DNA was isolated from 61 oligodendroglial tumors for analysis of methylation using methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). We correlated methylation status with clinicopathological findings and outcome. The genes found to be most frequently methylated in oligodendroglial tumors were RASSF1A (80.3%), CASP8 (70.5%), and CDKN2A (52.5%). Kaplan-Meier survival curve analysis demonstrated longer duration of progression-free survival in patients with 19q loss, aged less than 38 years, and with a proliferative index of less than 5%. Methylation of the ESR1 promoter is significantly associated with shorter duration of overall survival and progression-free survival, and that methylation of IGSF4 and RASSF1A is significantly associated with shorter duration of progression-free survival. However, none of the methylation status of ESR1, IGSF4, and RASSF1A was of prognostic value for survival in a multivariate Cox model. A number of novel and interesting epigenetic alterations were identified in this study. The findings highlight the importance of methylation profiles in oligodendroglial tumors and their possible involvement in tumorigenesis.
异常甲基化与多种人类肿瘤中肿瘤相关基因的转录失活有关。DNA甲基化在少突胶质细胞瘤中的影响尚未完全明确。从61例少突胶质细胞瘤中分离出基因组DNA，采用甲基化特异性多重连接依赖探针扩增法（MS-MLPA）分析甲基化情况。我们将甲基化状态与临床病理特征及预后相关联。在少突胶质细胞瘤中发现最常发生甲基化的基因是RASSF1A（80.3%）、CASP8（70.5%）和CDKN2A（52.5%）。Kaplan-Meier生存曲线分析表明，19号染色体长臂缺失、年龄小于38岁且增殖指数小于5%的患者无进展生存期更长。雌激素受体1（ESR1）启动子甲基化与总生存期和无进展生存期缩短显著相关，免疫球蛋白超家族成员4（IGSF4）和RASSF1A甲基化与无进展生存期缩短显著相关。然而，在多变量Cox模型中，ESR1、IGSF4和RASSF1A的甲基化状态均对生存无预后价值。本研究发现了一些新的且有趣的表观遗传改变。这些发现凸显了甲基化谱在少突胶质细胞瘤中的重要性及其可能参与肿瘤发生的过程。
