Document Type

Article

Publication Date

1-1-2017

Publication Title

PLoS One

Keywords

Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Brain Neoplasms; China; Cohort Studies; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Dacarbazine; Ethnic Groups; Female; Glioma; Humans; Male; Middle Aged; Polymorphism, Single Nucleotide; Prognosis; Promoter Regions, Genetic; Survival Analysis; Temozolomide; Tumor Suppressor Proteins; Young Adult

Abstract

The methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) is associated with the prognosis in gliomas and in other cancers. Recent studies showed that rs16906252, an SNP in the MGMT promoter, is associated with promoter methylation and is a predictor of the overall survival time (OST) and the response to temozolomide (TMZ) treatment. However, these findings haven't been systematically investigated in the Han-Chinese population. We analyzed the relevance between rs16906252 polymorphisms, the MGMT methylation status, and the OST in 72 Han-Chinese gliomas patients. The MGMT promoter methylation was measured by bisulfite conversion followed by pyro-sequencing, while rs16906252 was measured by restriction endonuclease digestion. Contrary to the previous findings, we found no association between rs16906252 genotypes and promoter methylation on MGMT. The lower-grade glioma (LGGs) patients carrying the C allele with rs16906252 showed a surprisingly better OST (P = 0.04). Furthermore, the LGG patients carrying hypo-methylated MGMT promoter and rs16906252 T allele showed significantly poorer prognosis. The prognostic benefit of MGMT promoter methylation and genotypes on gliomas patients is marginal. A new molecular stratified patient grouping of LGGs is potentially associated with poorer OST. Active MGMT might have a protective role in LGG tumors, enabling evolution to severe malignancy.

Department

Institute for Systems Biology

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