A Hypermethylated Phenotype Is a Better Predictor of Survival than MGMT Methylation in Anaplastic Oligodendroglial Brain Tumors: A Report from EORTC Study 26951
| العنوان: | A Hypermethylated Phenotype Is a Better Predictor of Survival than MGMT Methylation in Anaplastic Oligodendroglial Brain Tumors: A Report from EORTC Study 26951 |
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| المؤلفون: | Lariesa Lapre, Pim J. French, Ahmed Idbaih, Thierry Gorlia, Lonneke A.M. Gravendeel, Johannes L. Teepen, Johan M. Kros, Marc Sanson, Martin J. van den Bent, Peter A. E. Sillevis Smitt, Pieter Wesseling |
| المساهمون: | Pathology, CCA - Innovative therapy, Neurology |
| المصدر: | van den Bent, M J, Gravendeel, L A, Gorlia, T, Kros, J M, Lapre, L, Wesseling, P, Teepen, J L, Idbaih, A, Sanson, M, Smitt, P A E S & French, P J 2011, ' A Hypermethylated Phenotype Is a Better Predictor of Survival than MGMT Methylation in Anaplastic Oligodendroglial Brain Tumors: A Report from EORTC Study 26951 ', Clinical Cancer Research, vol. 17, no. 22, pp. 7148-7155 . https://doi.org/10.1158/1078-0432.CCR-11-1274Test Clinical Cancer Research, 17(22), 7148-7155. American Association for Cancer Research Inc. Clinical Cancer Research, 17, 22, pp. 7148-7155 Clinical Cancer Research, 17, 7148-7155 |
| بيانات النشر: | American Association for Cancer Research Inc., 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Male, Cancer Research, Adolescent, medicine.medical_treatment, Oligodendroglioma, Biology, Astrocytoma, Bioinformatics, SDG 3 - Good Health and Well-being, medicine, Humans, Oligodendroglial Tumor, Promoter Regions, Genetic, DNA Modification Methylases, neoplasms, Aged, Chemotherapy, Temozolomide, Brain Neoplasms, Tumor Suppressor Proteins, Histology, Methylation, DNA Methylation, Middle Aged, Prognosis, Phenotype, Translational research Tissue engineering and pathology [ONCOL 3], digestive system diseases, DNA Repair Enzymes, Oncology, DNA methylation, Cancer research, Female, Mgmt methylation, medicine.drug |
| الوصف: | Purpose: The MGMT promoter methylation status has been suggested to be predictive for outcome to temozolomide chemotherapy in patients with glioblastoma (GBM). Subsequent studies indicated that MGMT promoter methylation is a prognostic marker even in patients treated with radiotherapy alone, both in GBMs and in grade III gliomas. Experimental Design: To help determine the molecular mechanism behind this prognostic effect, we have conducted genome-wide methylation profiling and determined the MGMT promoter methylation status, 1p19q LOH, IDH1 mutation status, and expression profile on a series of oligodendroglial tumors [anaplastic oligodendrogliomas (AOD) and anaplastic oligoastrocytomas (AOA)] within EORTC study 26951. The series was expanded with tumors of the same histology and treatment from our own archive. Results: Methylation profiling identified two main subgroups of oligodendroglial brain tumors of which survival in the CpG island hypermethylation phenotype (CIMP+) subgroup was markedly better than the survival of the unmethylated (CIMP−) subgroup (5.62 vs. 1.24 years; P < 0.0001). CIMP status correlated with survival, MGMT promoter methylation, 1p19q LOH, and IDH1 mutation status. CIMP status strongly increases the predictive accuracy of survival in a model including known clinical prognostic factors such as age and performance score. We validated our results on an independent data set from the Cancer Genome Atlas (TCGA). Conclusion: The strong association between CIMP status and MGMT promoter methylation suggests that the MGMT promoter methylation status is part of a more general, prognostically favorable genome-wide methylation profile. Methylation profiling therefore may help identify AODs and AOAs with improved prognosis. Clin Cancer Res; 17(22); 7148–55. ©2011 AACR. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::68b7d813d98ed68bea2fc753b52cbc7aTest https://pure.eur.nl/en/publications/8b4a113b-2d48-4ae4-a2c1-47ae30bc638fTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....68b7d813d98ed68bea2fc753b52cbc7a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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