The Isocitrate Dehydrogenase mutation- and O6-methylguanine-DNA-methyltransferase promotor methylation status of glioblastomas at Groote Schuur Hospital
| dc.contributor.advisor | Singh, Shivani | |
| dc.contributor.advisor | Ikumi, Nadia | |
| dc.contributor.author | Rocher, Wilhelmus Diederiks | |
| dc.date.accessioned | 2026-08-05T12:42:42Z | |
| dc.date.available | 2026-08-05T12:42:42Z | |
| dc.date.issued | 2026 | |
| dc.date.updated | 2026-08-05T12:38:16Z | |
| dc.description.abstract | Background: Glioblastoma (GBM) isocitrate dehydrogenase (IDH) wild type (IDHwt) and high grade astrocytoma (HGA) IDH mutant (IDHmt), WHO CNS grade 4, represents the most common primary malignant brain tumours in adults. Both tumours have a poor prognosis, with a median survival of 12 to 14 months. In 2021 the World Health Organization (WHO) updated the classification of high grade gliomas separating tumours based on their IDH mutation status, to guide prognosis and treatment. Furthermore, these lesions can be divided by their eligibility for alkylating chemotherapeutic drugs, such as Temozolomide (TMZ), based on their O6-methylguanine-DNA-methyltransferase (MGMT) methylation status. Aim: The aim of this study is to reclassify tumours diagnosed as GBM between 2016 and 2019, before the advent of the current WHO recommendations, according to their IDH mutation status, as well as to determine the MGMT methylation status of these lesions to possibly advocate for the use of TMZ in our setting. These results will then be compared to international studies to determine if the patients in our cohort have similar demographics related to the different types of high grade gliomas. Methods: Patients diagnosed with glioblastoma at Groote Schuur Hospital, between 2016 and 2019 were reviewed following data retrieval from TrakCare LAB as well as retrieval and review of histology slides and immunohistochemistry when available. Tissue blocks of the patients reviewed were collected and sent to Inqaba Biotech for DNA extraction, IDH sequencing and MGMT methylation studies. The results were then correlated with the newest WHO classification, assessed for TMZ eligibility and correlated with international studies. Results: After exclusion criteria was applied a total of 45 cases were reviewed, with 21 females and 24 males making up the cohort, with ages ranging between 21 years old and 76 years old (median 55 years). Radiological imaging analyses suggested that most tumours occur in the frontal and temporal lobes with right side predominance. IDH-mutation status, as determined by both immunohistochemistry and sequencing, was identified in three cases. Of the 32 patients who had methylation studies, 25 (78%) were MGMT methylated according to EpiTYPER data. Discussion: According to our data 29 cases were not tested for IDH mutation by immunohistochemistry, mostly prior to 2018, mirroring the WHO recommendations of the time. With the combination of immunohistochemistry and sequencing data 3 cases can be reclassified as HGA IDHmt, with the remainder of the cases classified as GBM IDHwt. In our cohort 25 patients would have benefitted from TMZ therapy. HGA IDHmt occurred in younger patients (50 years of age or less), correlating with current international data. Limitations of the study were the inability to correlate immunohistochemistry with sequencing data as well as the decreased yield of DNA on paraffin embedded tissue, which made sequencing and methylation studies impossible on some of the samples. Conclusion: IDH mutation status is crucial for diagnosing high grade gliomas, for prognosis and treatment. Our cohort mirrors the global demographics and IDH mutation status of high grade gliomas. MGMT testing in our cohort showed potential benefits for some patients. | |
| dc.identifier.apacitation | Rocher, W. D. (2026). <i>The Isocitrate Dehydrogenase mutation- and O6-methylguanine-DNA-methyltransferase promotor methylation status of glioblastomas at Groote Schuur Hospital</i>. (). University of Cape Town ,Faculty of Health Sciences ,Department of Pathology. Retrieved from http://hdl.handle.net/11427/43704 | en_ZA |
| dc.identifier.chicagocitation | Rocher, Wilhelmus Diederiks. <i>"The Isocitrate Dehydrogenase mutation- and O6-methylguanine-DNA-methyltransferase promotor methylation status of glioblastomas at Groote Schuur Hospital."</i> ., University of Cape Town ,Faculty of Health Sciences ,Department of Pathology, 2026. http://hdl.handle.net/11427/43704 | en_ZA |
| dc.identifier.citation | Rocher, W.D. 2026. The Isocitrate Dehydrogenase mutation- and O6-methylguanine-DNA-methyltransferase promotor methylation status of glioblastomas at Groote Schuur Hospital. . University of Cape Town ,Faculty of Health Sciences ,Department of Pathology. http://hdl.handle.net/11427/43704 | en_ZA |
| dc.identifier.ris | TY - Thesis / Dissertation AU - Rocher, Wilhelmus Diederiks AB - Background: Glioblastoma (GBM) isocitrate dehydrogenase (IDH) wild type (IDHwt) and high grade astrocytoma (HGA) IDH mutant (IDHmt), WHO CNS grade 4, represents the most common primary malignant brain tumours in adults. Both tumours have a poor prognosis, with a median survival of 12 to 14 months. In 2021 the World Health Organization (WHO) updated the classification of high grade gliomas separating tumours based on their IDH mutation status, to guide prognosis and treatment. Furthermore, these lesions can be divided by their eligibility for alkylating chemotherapeutic drugs, such as Temozolomide (TMZ), based on their O6-methylguanine-DNA-methyltransferase (MGMT) methylation status. Aim: The aim of this study is to reclassify tumours diagnosed as GBM between 2016 and 2019, before the advent of the current WHO recommendations, according to their IDH mutation status, as well as to determine the MGMT methylation status of these lesions to possibly advocate for the use of TMZ in our setting. These results will then be compared to international studies to determine if the patients in our cohort have similar demographics related to the different types of high grade gliomas. Methods: Patients diagnosed with glioblastoma at Groote Schuur Hospital, between 2016 and 2019 were reviewed following data retrieval from TrakCare LAB as well as retrieval and review of histology slides and immunohistochemistry when available. Tissue blocks of the patients reviewed were collected and sent to Inqaba Biotech for DNA extraction, IDH sequencing and MGMT methylation studies. The results were then correlated with the newest WHO classification, assessed for TMZ eligibility and correlated with international studies. Results: After exclusion criteria was applied a total of 45 cases were reviewed, with 21 females and 24 males making up the cohort, with ages ranging between 21 years old and 76 years old (median 55 years). Radiological imaging analyses suggested that most tumours occur in the frontal and temporal lobes with right side predominance. IDH-mutation status, as determined by both immunohistochemistry and sequencing, was identified in three cases. Of the 32 patients who had methylation studies, 25 (78%) were MGMT methylated according to EpiTYPER data. Discussion: According to our data 29 cases were not tested for IDH mutation by immunohistochemistry, mostly prior to 2018, mirroring the WHO recommendations of the time. With the combination of immunohistochemistry and sequencing data 3 cases can be reclassified as HGA IDHmt, with the remainder of the cases classified as GBM IDHwt. In our cohort 25 patients would have benefitted from TMZ therapy. HGA IDHmt occurred in younger patients (50 years of age or less), correlating with current international data. Limitations of the study were the inability to correlate immunohistochemistry with sequencing data as well as the decreased yield of DNA on paraffin embedded tissue, which made sequencing and methylation studies impossible on some of the samples. Conclusion: IDH mutation status is crucial for diagnosing high grade gliomas, for prognosis and treatment. Our cohort mirrors the global demographics and IDH mutation status of high grade gliomas. MGMT testing in our cohort showed potential benefits for some patients. DA - 2026 DB - OpenUCT DP - University of Cape Town KW - anatomical pathology LK - https://open.uct.ac.za PB - University of Cape Town PY - 2026 T1 - The Isocitrate Dehydrogenase mutation- and O6-methylguanine-DNA-methyltransferase promotor methylation status of glioblastomas at Groote Schuur Hospital TI - The Isocitrate Dehydrogenase mutation- and O6-methylguanine-DNA-methyltransferase promotor methylation status of glioblastomas at Groote Schuur Hospital UR - http://hdl.handle.net/11427/43704 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/43704 | |
| dc.identifier.vancouvercitation | Rocher WD. The Isocitrate Dehydrogenase mutation- and O6-methylguanine-DNA-methyltransferase promotor methylation status of glioblastomas at Groote Schuur Hospital. []. University of Cape Town ,Faculty of Health Sciences ,Department of Pathology, 2026 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/43704 | en_ZA |
| dc.language.iso | en | |
| dc.language.rfc3066 | eng | |
| dc.publisher.department | Department of Pathology | |
| dc.publisher.faculty | Faculty of Health Sciences | |
| dc.publisher.institution | University of Cape Town | |
| dc.subject | anatomical pathology | |
| dc.title | The Isocitrate Dehydrogenase mutation- and O6-methylguanine-DNA-methyltransferase promotor methylation status of glioblastomas at Groote Schuur Hospital | |
| dc.type | Thesis / Dissertation | |
| dc.type.qualificationlevel | Masters | |
| dc.type.qualificationlevel | MMed |