Survival curves stratified by rs1625649 genotypes in patients with <i>MGMT</i> methylated GBM.

<p>(A) Progression-free survival and (B) overall survival of the study cohort. Patients with homozygous rs1625649 (AA genotype) had longer progression-free survival than those with heterozygous (CA genotype) or wild type (CC genotype) rs1625649. However, the difference in overall survival did not reach statistical significance.</p

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

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

Association between rs1625649 genotypes, <i>MGMT</i> status and clinical characteristics.

<p>Association between rs1625649 genotypes, <i>MGMT</i> status and clinical characteristics.</p

Association between rs1625649 genotypes and MGMT status subgrouped by promoter methylation (qMSP) and protein expression (IHC).

<p>Association between rs1625649 genotypes and MGMT status subgrouped by promoter methylation (qMSP) and protein expression (IHC).</p

Multivariate analyses of progression-free survival and overall survival stratified by rs1625649 genotypes in patients with <i>MGMT</i> methylated glioblastoma.

<p>Multivariate analyses of progression-free survival and overall survival stratified by rs1625649 genotypes in patients with <i>MGMT</i> methylated glioblastoma.</p