O6-methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastoma

• Main Authors: Ali H. Alassiri, Ali Alkhaibary, Saud Al-Sarheed, Fahd Alsufani, Mohammed Alharbi, Ahmed Alkhani, Ahmed Aloraidi
• Format: Article
• Language: English
• Published: King Faisal Specialist Hospital and Research Centre 2019-12-01
• Series: Annals of Saudi Medicine
• Online Access: https://www.annsaudimed.net/doi/full/10.5144/0256-4947.2019.410

BACKGROUND: Treatment of glioblastoma (GB), the most common malignant primary brain tumor in adults, can include alkylating chemo-therapeutic agents. Two molecular biomarkers of treatment response are MGMT (O6-methylguanine-DNA methyltransferase) promoter methylation and IDH (isocitrate dehydrogenase) mutations, which prevent repair of tumor cell DNA damage caused by alkylating chemotherapy. The status of MGMT promoter methylation and IDH mutation are associated with longer survival and a better response to chemotherapy. OBJECTIVE: Assess the prognostic value of MGMT methylation status and IDH mutation in adult Saudi glioblastoma patients. DESIGN: Retrospective, comparative survival analysis. SETTING: Tertiary care center. PATIENTS AND METHODS: The status of the MGMT promoter methylation and IDH mutation was assessed in adult patients diagnosed with GB between 2006 and 2019. A PCR-based assay was used to analyze for methylation of the MGMT promoter. A qualitative assay combining PCR clamping and amplification refractory mutation system technology was used to search for any of the 12 most common mutations in IDH1 and IDH2. Differences in survival were compared between those with and without MGMT promoter methylation and IDH mutation and between other subgroups. MAIN OUTCOME MEASURES: Survival of GB patients relative to MGMT promoter methylation and IDH mutation status. SAMPLE SIZE: 146 patients (80 males and 66 females). RESULTS: Of 43 (29.5%) cases tested for MGMT promoter methylation, 14 (32.5%) were positive. Of 65 (44.5%) cases screened for IDH mutation, 6 cases (9.2%) tested positive. The 36-month survival rate was 47% for the MGMT methylated cohort compared to 27% for their unmethylated counterparts. The 18-month survival rate for the IDH-mutant was 75% compared to 48% for their IDH-wildtype counterparts. CONCLUSION: The findings confirm the positive impact of both MGMT promoter methylation and IDH mutation on the overall survival of Saudi GB patients. LIMITATIONS: Single institute study with relatively few tested cases. CONFLICT OF INTEREST: None.