Primary Spinal Cord Oligodendroglioma with Postoperative Adjuvant Radiotherapy: A Case Report

Primary spinal cord oligodendrogliomas are rare tumors comprising two percent of all spinal cord tumors. Although a treatment guideline has yet to be established, maximal surgical resection is primary in the treatment of spinal cord oligodendrogliomas. Adjuvant radiotherapy has remained controversial, and it is unclear whether chemotherapy adds any benefit. In this case report, the authors present a 24-year-old male who had a seven-year history of left leg weakness and a radiating pain in both legs. Magnetic resonance image (MRI) showed an intramedullary mass at the T4-T8 level. He underwent subtotal removal of the tumor and pathologic diagnosis revealed a WHO grade II oligodendroglioma. The patient was treated with radiotherapy postoperatively and followed up with MRI annually. Clinical and radiological status of the patient had been stationary for four years after the surgery. The five-year follow-up MRI showed an increase in the size and extent of the residual tumor. Despite radiological progression, considering that symptoms and the performance status of the patient had remained unchanged, further treatment has not been performed. Given the clinical outcome of this patient, close observation after subtotal removal with adjuvant radiotherapy is one of the acceptable treatment options for WHO grade II spinal cord oligodendrogliomas.

Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma

OBJECTIVES: 1) To correlate the methylation status of the O6-methylguanine-DNA-methyltransferase (MGMT) promoter to its gene and protein expression levels in glioblastoma and 2) to determine the most reliable method for using MGMT to predict the response to adjuvant therapy in patients with glioblastoma. BACKGROUND: The MGMT gene is epigenetically silenced by promoter hypermethylation in gliomas, and this modification has emerged as a relevant predictor of therapeutic response. METHODS: Fifty-one cases of glioblastoma were analyzed for MGMT promoter methylation by methylation-specific PCR and pyrosequencing, gene expression by real time polymerase chain reaction, and protein expression by immunohistochemistry. RESULTS: MGMT promoter methylation was found in 43.1 percent of glioblastoma by methylation-specific PCR and 38.8 percent by pyrosequencing. A low level of MGMT gene expression was correlated with positive MGMT promoter methylation (p = 0.001). However, no correlation was found between promoter methylation and MGMT protein expression (p = 0.297). The mean survival time of glioblastoma patients submitted to adjuvant therapy was significantly higher among patients with MGMT promoter methylation (log rank = 0.025 by methylation-specific PCR and 0.004 by pyrosequencing), and methylation was an independent predictive factor that was associated with improved prognosis by multivariate analysis. DISCUSSION AND CONCLUSION: MGMT promoter methylation status was a more reliable predictor of susceptibility to adjuvant therapy and prognosis of glioblastoma than were MGMT protein or gene expression levels. Methylation-specific polymerase chain reaction and pyrosequencing methods were both sensitive methods for determining MGMT promoter methylation status using DNA extracted from frozen tissue.

Methylation Status of the O6-Methylguanine- Deoxyribonucleic Acid Methyltransferase Gene Promoter in World Health Organization Grade III Gliomas

OBJECTIVE: We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter in World Health Organization (WHO) grade III gliomas in association with other molecular markers to evaluate their prevalence. METHODS: The samples of a total of 36 newly WHO grade III glioma patients including 19 anaplastic oligodendrogliomas (AO), 7 anaplastic oligoastrocytomas (AOA), and 10 anaplastic astrocytomas (AA) were analyzed. The methylation status of the MGMT gene promoter was confirmed by methylation-specific polymerase chain reaction. The 1p/19q chromosomal deletion status and EGFR amplification were assessed by Fluorescence In-Situ Hybridization. MGMT, EGFR, EGFRvIII, and p53 expression were analyzed by immunohistochemical staining. RESULTS: The MGMT gene promoter was methylated in 32 (88.9%) and unmethylated in 4 (11.2%). Among them, all of the AO and AOA had methylated MGMT gene promoter without exception. Significant associations between MGMT gene promoter hypermethylation and 1p/19q deletion was observed (p = 0.003). Other molecular markers failed to show significant associations between MGMT gene promoter statuses. CONCLUSION: There was extensive epigenetic silencing of MGMT gene in high grade gliomas with oligodendroglial component. Together with frequent 1p/19q co-deletion in oligodendroglial tumors, this may add plausible explanations supporting the relative favorable prognosis in oligodendroglial tumors compared with pure astrocytic tumors.

Detection and significance of promoter hypermethylation of p16 gene and MGMT gene in plasma from non-small cell lung cancer patients / 肿瘤

Objective: To detect the aberrant methylation in the promoter of p 16 and O6-methylguanine DNA methyltransferase (MGMT) gene in peripheral plasma from non-small cell lung cancer (NSCLC) patients and to evaluate the clinical significance in the screening and early diagnosis of NSCLC. Methods: A nested methylation-specific PCR (nMSP) was performed for the detection of promoter hypermethylation of p16 gene and MGMT gene in plasma from 65 NSCLC patients. Results: Of the 65 plasma samples, p16 gene promoter hypermethylation was detected in 19 patients (29.23%) and MGMT gene promoter hypermethylation was found in 16 patients (24.62%). However, promoter hypermethylation in p16 gene and MGMT gene was not found in plasma samples from the normal controls (P 0.05). Conclusion: Detection of the aberrant methylation in the promoter of p16 gene and MGMT gene in plasma from NSCLC patients by nMSP method might provide valuable information for the screening, early diagnosis, and prediction of prognosis of NSCLC.

Inhibition of MGMT gene by hairpin siRNA expression vector in vitro / 第三军医大学学报

Objective To construct the small interfering RNA (siRNA) eukaryotic expression vector specific to human MGMT gene(pRNATin-H1.2/Neo MGMT siRNA) to observe its silencing effect on MGMT gene in vitro.Methods The pRNATin-H1.2/Neo MGMT siRNA expression vector was constructed by gene recombination,then transfected into the cultured HelaS3 cells.Inhibitory effect of siRNAs was detected by semi-quantitative RT-PCR.Results The pRNATin-H1.2/Neo MGMT siRNA expression vector was successfully constructed.Cells transfected with pRNATin-H1.2/Neo MGMT siRNA could obviously inhibit the expression level of MGMT gene.Conclusion The pRNATin-H1.2/Neo MGMT siRNA expression vector could inhibit the MGMT gene expression.