The MGMT promoter single-nucleotide polymorphism rs1625649 had prognostic impact on patients with MGMT methylated glioblastoma

PLoS One. 2017 Oct 16;12(10):e0186430. doi: 10.1371/journal.pone.0186430. eCollection 2017.

Abstract

Promoter methylation is the most significant mechanism to regulate O6-methylguanine-DNA-methyltransferase (MGMT) expression. Single-nucleotide polymorphisms (SNPs) in the MGMT promoter region may also play a role. The aim of this study was to evaluate the clinical significance of SNPs in the MGMT promoter region of glioblastoma. Genomic DNAs from 118 glioblastomas were collected for polymerase chain reaction (PCR) amplification. Sanger sequencing was used to sequence the MGMT promoter region to detect SNPs. The results were correlated with MGMT status and patient survival. Rs1625649 was the only polymorphic SNP located at the MGMT promoter region in 37.5% of glioblastomas. Homozygous rs1625649 (AA genotype) was correlated with a higher MGMT methylation level and a lower protein expression, but the result was not statistically significant. In patients with MGMT methylated glioblastoma, cases with homozygous rs1625649 (AA genotype) were significantly associated with a lack of MGMT protein expression and a better progression-free survival (PFS) than the cases with wild type rs1625649 (CC genotype) or heterozygous rs1625649 (CA genotype). The survival impact was significant in multivariate analyses. In conclusion, the MGMT promoter homozygous rs1625649 (AA genotype) was found to correlate with a better PFS in patients with MGMT methylated glioblastoma.

MeSH terms

  • DNA Methylation*
  • DNA Modification Methylases / genetics*
  • DNA Repair Enzymes / genetics*
  • Female
  • Glioblastoma / diagnosis*
  • Glioblastoma / genetics*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Survival Analysis
  • Tumor Suppressor Proteins / genetics*

Substances

  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes

Grants and funding

The authors CYH and DMH received funding from " Taipei Veterans General Hospital, Grant Number: V104C-187, V105C-185, V105C-187 (https://www.vghtpe.gov.tw/Index.action)"; and from “The Ministry of Science and Technology, Executive Yuan, R.O.C., Grant Number: MOST 104-2320-B-075-003, MOST 104-2320-B-075-004 (https://www.most.gov.tw/)”. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.