O6-methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastoma
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 dehydrogenas...
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doaj-88bd11a8c7fc466186c30460d7014d172020-11-25T02:38:39ZengKing Faisal Specialist Hospital and Research CentreAnnals of Saudi Medicine0256-49470975-44662019-12-0139641041610.5144/0256-4947.2019.41010.5144_0256-4947.2019.410O6-methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastomaAli H. Alassiri0Ali Alkhaibary1Saud Al-Sarheed2Fahd Alsufani3Mohammed Alharbi4Ahmed Alkhani5Ahmed Aloraidi6From the College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaFrom the College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaFrom the College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaFrom the Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi ArabiaFrom the Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi ArabiaFrom the Department of Neurosurgery, King Abdulaziz Medical City, Riyadh, Saudi ArabiaFrom the Department of Neurosurgery, King Abdulaziz Medical City, Riyadh, Saudi ArabiaBACKGROUND: 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.https://www.annsaudimed.net/doi/full/10.5144/0256-4947.2019.410 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ali H. Alassiri Ali Alkhaibary Saud Al-Sarheed Fahd Alsufani Mohammed Alharbi Ahmed Alkhani Ahmed Aloraidi |
spellingShingle |
Ali H. Alassiri Ali Alkhaibary Saud Al-Sarheed Fahd Alsufani Mohammed Alharbi Ahmed Alkhani Ahmed Aloraidi O6-methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastoma Annals of Saudi Medicine |
author_facet |
Ali H. Alassiri Ali Alkhaibary Saud Al-Sarheed Fahd Alsufani Mohammed Alharbi Ahmed Alkhani Ahmed Aloraidi |
author_sort |
Ali H. Alassiri |
title |
O6-methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastoma |
title_short |
O6-methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastoma |
title_full |
O6-methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastoma |
title_fullStr |
O6-methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastoma |
title_full_unstemmed |
O6-methylguanine-DNA methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of Saudi patients with glioblastoma |
title_sort |
o6-methylguanine-dna methyltransferase promoter methylation and isocitrate dehydrogenase mutation as prognostic factors in a cohort of saudi patients with glioblastoma |
publisher |
King Faisal Specialist Hospital and Research Centre |
series |
Annals of Saudi Medicine |
issn |
0256-4947 0975-4466 |
publishDate |
2019-12-01 |
description |
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. |
url |
https://www.annsaudimed.net/doi/full/10.5144/0256-4947.2019.410 |
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