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An Analysis Of The Correlation Between Mgmt Promoter Methylation And Gene Expression In Glioma Patients Of Chinese

Posted on:2015-03-26Degree:MasterType:Thesis
Country:ChinaCandidate:J H YangFull Text:PDF
GTID:2254330428477211Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Glioma is the most common nervous system tumors in adults. The mortality rate of glioma is high. The treatment of glioma is a worldwide problem. Alkyl compounds—temozolomid is a new kind of imidazotetrazine drugs. It has broad-spectrum anti-tumor activity on human tumor cell lines. The United States and the European medical community have defined temozolomid as a "gold standard" to treat malignant brain tumor and the International Medical Community has defined temozolomide as a first-line drugs for treatment of malignant brain tumors.The full name of MGMT is06-methylguanine-DNA methyltransferese and it is a highly efficient DNA methyltransferese. The enzyme can transfer the alkyl group from DNA to its cysteine residue, repair DNA alkylation damage caused by a variety of alkylating agents, especially O6-methylguanine in the DNA molecule, and prevent cancer and cell death. In addition, in the process of the treatment of patients with glioma, MGMT excess expression can resist temozolomid. MGMT gene promoter hypermethylation can result in a decline in the gene transcription level, and reduce MGMT protein expression in cells. Therefore, MGMT methylation modification as a prediction for temozolomid sensitive molecular marker is widely used.At present, MGMT promoter methylaiton (CpG135and137) has been shown to be an important biomarker in predicting the glioma patient’s responsiveness to temozolomide. However, a number of clinical studies suggested that the two CpG sites failed to correlate with patient’s outcome. It will lead to inaccurate prediction of drug sensitivity. Therefore, searching for the more accurate methylation sites is very important.This paper adopted a new gene methylation detection technology—Pyrosequencing, established a quantitative detection method which can detect all of the methylation sites in the MGMT gene promoter region. This study detected15cases of glioma patients and293cell lines of all of the MGMT gene promoter methylation sites. Though statistical tests, we found 35CpG sites which had significant difference. Then, we used the method of real-time quantitative PCR to analyze the expression of MGMT gene. Eight CpG sites which had obvious relationship between methylation and expression were found by correlation analysis (P<0.0001). It is important to guide individualized treatment.Pyrosequencing has been evaluated as a "gold standard" to detect methylation, it has high sensitivity, short cycle time, and enables the detection of individual CpG site or more consecutive sites for quantitative analysis.
Keywords/Search Tags:CpG island methylation, glioma, MGMT, pyro sequencing
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