P16 PROMOTER METHYLATION IN THE SERUM AS A BASIS FOR THE MOLECULAR DIAGNOSIS OF GLIOMAS
P16 PROMOTER METHYLATION IN THE SERUM AS A BASIS FOR THE MOLECULAR DIAGNOSIS OF GLIOMAS
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DOI：
10.1227/01.neu.0000340683.19920.e3
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发表时间：
2009-03
期刊：
影响因子：
4.8
通讯作者：
T. Wakabayashi;A. Natsume;H. Hatano;M. Fujii;S. Shimato;Motokazu Ito;Masasuke Ohno;S. Ito;M. Ogura;J. Yoshida
中科院分区：
文献类型：
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作者：
T. Wakabayashi;A. Natsume;H. Hatano;M. Fujii;S. Shimato;Motokazu Ito;Masasuke Ohno;S. Ito;M. Ogura;J. Yoshida
肿瘤起源的脱氧核糖核酸（DNA）甲基化可以在癌症患者的血清/血浆中检测到。本研究的目的是检测异常p16启动子甲基化作为一个潜在的诊断标志物在弥漫性胶质瘤患者的血清中，以区分胶质瘤，特别是区分那些在脑干从其他人，这是通过使用改良的甲基化特异性聚合酶链反应技术。方法应用甲基化特异性聚合酶链反应（methylation-specific polymerase chain reaction，PCR）检测20例星形细胞肿瘤和20例少突胶质细胞肿瘤组织及相应血清标本中p16基因甲基化。以10例健康人血清为对照。分析脑胶质瘤患者血清中p16基因甲基化与临床病理特征的关系。此外，分析了7例脑干肿瘤患者（4例胶质瘤，1例神经鞘瘤，1例海绵状血管瘤和室管膜瘤）的血清DNA。我们在20例星形细胞瘤组织中发现12例（60%）p16甲基化，而在少突胶质细胞瘤组织中仅发现1例。在12例肿瘤组织异常甲基化的患者中，9例（75%）的血清中检测到类似的甲基化。在没有这些甲基化改变的肿瘤患者或10名健康对照的外周血清中未检测到甲基化的p16序列。此外，在所有脑干星形细胞瘤病例中均观察到血清中p16启动子甲基化，但在其他病例中未观察到。结论该方法有可能作为弥漫性胶质瘤的血清分子诊断技术。
OBJECTIVEDeoxyribonucleic acid (DNA) methylation of tumor origin can be detected in the serum/plasma of cancer patients. The aim of this study was to detect aberrant p16 promoter methylation as a potential diagnostic marker in the serum of patients with diffuse glioma to differentiate between gliomas and, particularly, to differentiate those in the brainstem from others; this was done by using the modified methylation-specific polymerase chain reaction technique. METHODSThe methylation-specific polymerase chain reaction was used to detect p16 methylation in the DNA extracted from 20 astrocytic tumors and 20 oligodendroglial tumors and the corresponding serum samples. Serum samples from 10 healthy individuals were used as controls. The association of p16 hypermethylation in the serum DNA of glioma patients with clinicopathological characteristics was analyzed. In addition, the serum DNA in 7 patients with a brainstem tumor (4 gliomas, 1 schwannoma, 1 cavernous angioma, and 1 ependymoma) was analyzed. RESULTSWe found p16 methylation in 12 (60%) of the 20 tissues with astrocytoma, but in only 1 of the tissues with oligodendroglioma. Similar methylations were detected in the serum of 9 (75%) of the 12 patients with aberrant methylation in the tumor tissues. No methylated p16 sequences were detected in the peripheral serum of the patients having tumors without these methylation changes or in the 10 healthy controls. Additionally, p16 promoter methylation in the serum was observed in all brainstem astrocytoma cases, but not in other cases. CONCLUSIONThis assay has potential for use as a serum-based molecular diagnosis technique for diffuse glioma.