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The tumoral A genotype of the MGMT rs34180180 single-nucleotide polymorphism in aggressive gliomas is associated with shorter patients' survival.
- Source :
-
Carcinogenesis [Carcinogenesis] 2016 Feb; Vol. 37 (2), pp. 169-176. Date of Electronic Publication: 2015 Dec 30. - Publication Year :
- 2016
-
Abstract
- Malignant gliomas are the most common primary brain tumors. Grade III and IV gliomas harboring wild-type IDH1/2 are the most aggressive. In addition to surgery and radiotherapy, concomitant and adjuvant chemotherapy with temozolomide (TMZ) significantly improves overall survival (OS). The methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter is predictive of TMZ response and a prognostic marker of cancer outcome. However, the promoter regions the methylation of which correlates best with survival in aggressive glioma and whether the promoter methylation status predictive value could be refined or improved by other MGMT-associated molecular markers are not precisely known. In a cohort of 87 malignant gliomas treated with radiotherapy and TMZ-based chemotherapy, we retrospectively determined the MGMT promoter methylation status, genotyped single nucleotide polymorphisms (SNPs) in the promoter region and quantified MGMT mRNA expression level. Each of these variables was correlated with each other and with the patients' OS. We found that methylation of the CpG sites within MGMT exon 1 best correlated with OS and MGMT expression levels, and confirmed MGMT methylation as a stronger independent prognostic factor compared to MGMT transcription levels. Our main finding is that the presence of only the A allele at the rs34180180 SNP in the tumor was significantly associated with shorter OS, independently of the MGMT methylation status. In conclusion, in the clinic, rs34180180 SNP genotyping could improve the prognostic value of the MGMT promoter methylation assay in patients with aggressive glioma treated with TMZ.<br /> (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Adult
Brain Neoplasms mortality
Brain Neoplasms pathology
DNA Methylation genetics
Female
Genotype
Glioma mortality
Glioma pathology
Humans
Kaplan-Meier Estimate
Male
Polymerase Chain Reaction
Polymorphism, Restriction Fragment Length
Prognosis
Promoter Regions, Genetic genetics
Proportional Hazards Models
Retrospective Studies
Brain Neoplasms genetics
DNA Modification Methylases genetics
DNA Repair Enzymes genetics
Glioma genetics
Polymorphism, Single Nucleotide
Tumor Suppressor Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 37
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 26717998
- Full Text :
- https://doi.org/10.1093/carcin/bgv251