Prognostic significance of genome-wide DNA methylation profiles within the randomised, phase 3, EORTC CATNON trial on non-1p/19q deleted anaplastic glioma
dc.contributor.author | Tesileanu, C. M. S. | |
dc.contributor.author | van den Bent, M. J. | |
dc.contributor.author | Sanson, M. | |
dc.contributor.author | Wick, W. | |
dc.contributor.author | Brandes, A. A. | |
dc.contributor.author | Clement, P. M. | |
dc.contributor.author | Erridge, S. C. | |
dc.contributor.author | Vogelbaum, M. A. | |
dc.contributor.author | Nowak, A. K. | |
dc.contributor.author | Baurain, J. F. | |
dc.contributor.author | Mason, W. P. | |
dc.contributor.author | Wheeler, H. | |
dc.contributor.author | Chinot, O. L. | |
dc.contributor.author | Gill, S. | |
dc.contributor.author | Griffin, M. | |
dc.contributor.author | Rogers, L. | |
dc.contributor.author | Taal, W. | |
dc.contributor.author | Rudà, R. | |
dc.contributor.author | Weller, M. | |
dc.contributor.author | McBain, Catherine A | |
dc.contributor.author | van Linde, M. E. | |
dc.contributor.author | Sabedot, T. S. | |
dc.contributor.author | Hoogstrate, Y. | |
dc.contributor.author | von Deimling, A. | |
dc.contributor.author | de Heer, I. | |
dc.contributor.author | Brouwer, R. W. W. | |
dc.contributor.author | Aldape, K. | |
dc.contributor.author | Jenkins, R. B. | |
dc.contributor.author | Dubbink, H. J. | |
dc.contributor.author | Kros, J. M. | |
dc.contributor.author | Wesseling, P. | |
dc.contributor.author | Cheung, K. J. | |
dc.contributor.author | Golfinopoulos, V. | |
dc.contributor.author | Baumert, B. G. | |
dc.contributor.author | Gorlia, T. | |
dc.contributor.author | Noushmehr, H. | |
dc.contributor.author | French, P. J. | |
dc.contributor.author | van Ijken, WJF | |
dc.date.accessioned | 2021-05-18T08:48:10Z | |
dc.date.available | 2021-05-18T08:48:10Z | |
dc.date.issued | 2021 | en |
dc.identifier.citation | Tesileanu CMS, van den Bent MJ, Sanson M, Wick W, Brandes AA, Clement PM, et al. Prognostic significance of genome-wide DNA methylation profiles within the randomised, phase 3, EORTC CATNON trial on non-1p/19q deleted anaplastic glioma. Neuro-Oncology. 2021 Apr 29 | en |
dc.identifier.pmid | 33914057 | en |
dc.identifier.doi | 10.1093/neuonc/noab088 | en |
dc.identifier.uri | http://hdl.handle.net/10541/624023 | |
dc.description.abstract | Background: Survival in patients with IDH1/2 mutant (mt) anaplastic astrocytomas is highly variable. We have used the prospective phase 3 CATNON trial to identify molecular factors related to outcome in IDH1/2mt anaplastic astrocytoma patients. Methods: The CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant temozolomide. The presence of necrosis and/or microvascular proliferation was scored at central pathology review. Infinium MethylationEPIC BeadChip arrays were used for genome-wide DNA methylation analysis and the determination of copy number variations (CNV). Two DNA methylation-based tumour classifiers were used for risk stratification. Next-generation sequencing (NGS) was performed using one of two glioma-tailored NGS panels. The primary endpoint was overall survival measured from date of randomization. Results: Full analysis (genome-wide DNA methylation and NGS) was successfully performed on 654 tumours. Of these, 432 tumours were IDH1/2mt anaplastic astrocytomas. Both epigenetic classifiers identified poor prognosis patients that partially overlapped. A predictive prognostic Cox proportional hazards model identified that independent prognostic factors for IDH1/2mt anaplastic astrocytoma patients included; age, mini-mental state examination score, treatment with concurrent and/or adjuvant temozolomide, the epigenetic classifiers, PDGFRA amplification, CDKN2A/B homozygous deletion, PI3K mutations and total CNV load. Independent recursive partitioning analysis highlights the importance of these factors for patient prognostication. Conclusion: Both clinical and molecular factors identify IDH1/2mt anaplastic astrocytoma patients with worse outcome. These results will further refine the current WHO criteria for glioma classification | en |
dc.language.iso | en | en |
dc.relation.url | https://dx.doi.org/10.1093/neuonc/noab088 | en |
dc.title | Prognostic significance of genome-wide DNA methylation profiles within the randomised, phase 3, EORTC CATNON trial on non-1p/19q deleted anaplastic glioma | en |
dc.type | Article | en |
dc.contributor.department | Neurology Department, Erasmus MC, Rotterdam, the Netherlands | en |
dc.identifier.journal | Neuro Oncology | en |
dc.description.note | en |