title: MGMTpromoter methylation in serum and cerebrospinal fluid as a tumor-specific biomarker of glioma.
abstract: O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is a conventional technique to predict the prognosis or individualized treatment of glioma in tumor tissue following surgery or biopsy. However, the technique cannot be applied in those glioma patients with concomitant neurological dysfunctions or advanced age. The present study aimed to find a new minimally invasive and efficient alternative method for the detection ofMGMTpromoter methylation. The expression ofMGMTpromoter methylation was assessed in peripheral blood and cerebrospinal fluid (CSF), and compared to the corresponding tumor tissue from glioma patients. The 89 patients in the study [32 World Health Organization (WHO) grade II, 19 WHO grade III and 38 WHO grade IV) were pathologically-diagnosed glioma and received radiation therapy following sample collection. The resected glioma tumor tissue (89), corresponding serum (89) and CSF (78) samples were collected for the detection ofMGMTpromoter methylation using methylation-specific polymerase chain reaction. The sensitivity and specificity of detectingMGMTpromoter methylation in CSF and serum were compared. Among the tumor tissue samples, 51/89 (57.3%) showedMGMTpromoter methylation. The specificity of the detection in the CSF and serum samples reached 100%. The sensitivity ofMGMTpromoter methylation detection in CSF and serum were 26/40 (65.0%) and 19/51 (37.3%), respectively (P<0.05). In the WHO II, III and IV subgroups, the sensitivities ofMGMTpromoter methylation detection using CSF were 8/12 (66.7%), 11/18 (61.1%) and 7/10 (70.0%), respectively, which were significantly higher than the sensitivities using serum (7/21, 33.3%; 7/19, 36.8%; and 5/11, 45.5%, respectively P<0.05). Among patients with residual postoperative tumors, the sensitivities of detectingMGMTpromoter methylation using CSF and serum were 18/25 (72.0%) and 10/24 (41.7%), respectively, both of which were significantly higher than the corresponding values for patients without residual tumors (8/15, 53.3% and 6/19, 31.6%, respectively; P<0.05). The detection ofMGMTpromoter methylation in CSF specimens shows higher sensitivity compared to the serum for glioma patients. Assessment ofMGMTpromoter methylation in CSF may provide a promising clinical methodology for early diagnosis, individual treatment, monitoring of recurrence and prognosis for glioma patients.
authors.affiliation: Department of Radiation Oncology, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Radiation Oncology, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Radiation Oncology, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Cong
authors.affiliation: Department of Radiation Oncology, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: DU
authors.affiliation: Department of Radiation Oncology, Tianjin Huanhu Hospital, Tianjin 300060, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Song
keywords: O6-methylguanine-DNA methyltransferase; cerebrospinal fluid; circulating DNA; glioma; tumor-specific molecular marker