1p/19q LOH And Promoter Methylation Of DNA Repair Gene MGMT Guided Treatment For Malignant Gliomas

Recently, large scale genome-wide surveys have been used to identify newbiomarkers, leading to an increasing use of molecular markers in the assessment andmanagement of adult gliomas, including pathological classification of gliomas,estimating patient’s prognosis, and predicting treatment responses, which can guidesurgeons to decide correct treatment and avoid excessive or insufficient therapytreatment.Malignant gliomas include anaplastic oligodendroglioma, anaplastic astrocytoma,anaplastic oligodendrogliomas astrocytoma and glioblastoma. Guided by the principleof maximal safe resection in surgical procedure, glioblastoma patients are given theadjuvant treatment of concurrent TMZ and radiotherapy followed by adjuvant TMZ.However, the adjuvant therapy for anaplastic gliomas is undefined. Cairncross reportedthat loss of1p (and combined loss of1p and19q) resulted in a better prediction oftreatment responses to PCV chemotherapy and a longer survival in patients withanaplastic oligodendroglioma. Subsequent studies confirmed the prognostic andpredictive utility of1p/19q codeletion.TMZ is the second generation of alkylating agents, and it has been used for gliomachemotherapy because it can easily pass the blood-brain barrier and has low toxic sideeffects. MGMT gene encodes a DNA repair protein that removes alkyl groups from theO6position of guanine, an important site of DNA alkylation. Gene silencing inglioblastoma is commonly accompanied by methylation of promoter CpG islands,suggesting that methylation mediates MGMT silencing in human glioblastoma.Correlation with prognosis was also reported in anaplastic gliomas.Objective: To observe the clinical effect of individualized therapy for15patientswith malignant gliomas guided by1p/19q LOH and Promoter methylation of DNARepair Gene MGMT. Methods: Fifteen cases with malignant glioma who received endoscopic operationresection from July2012to January2013were collected in our study. The LOH ofchromosome1p/19q was investigated by PCR-based microsatellite analysis, MGMTpromoter methylation status was detected by MSP. The choice of adjuvant therapy foranaplastic gliomas depended on the status of1p/19q LOH and MGMT promotermethylation. The curative effects were evaluated based on response evaluation criteriain solid tumors (RECIST)Results: Among15cases,5cases were in complete remission (CR),9casesachieved partial remission (PR), and0case was with stable disease (SD),1case waswith progressive disease (PD). The objective response rate was93.3%(14/15) anddisease control rate was93.3%(14/15).Conclusion: Malignant gliomas obtain better clinical efficacy guided by1p/19qLOH and Promoter methylation of MGMT.