Methylation array profiling of adult brain tumours

• Verfasst von: Jaunmuktane, Zane [VerfasserIn]
• Verfasst von: Jones, David T. W. [VerfasserIn]
• Verfasst von: Schrimpf, Daniel [VerfasserIn]
• Verfasst von: Sill, Martin [VerfasserIn]
• Verfasst von: Pfister, Stefan [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Titel: Methylation array profiling of adult brain tumours
• Titelzusatz: diagnostic outcomes in a large, single centre
• Verf.angabe: Zane Jaunmuktane, David Capper, David T.W. Jones, Daniel Schrimpf, Martin Sill, Monika Dutt, Nirosha Suraweera, Stefan M. Pfister, Andreas von Deimling and Sebastian Brandner
• E-Jahr: 2019
• Jahr: 20 February 2019
• Umfang: 18 S.
• Teil: volume:7
• Teil: year:2019
• Teil: elocationid:24
• Teil: pages:1-18
• Teil: extent:18
• Fussnoten: Gesehen am 25.07.2019
• Titel Quelle: Enthalten in: Acta Neuropathologica Communications
• Ort Quelle: London : Biomed Central, 2013
• Jahr Quelle: 2019
• Band/Heft Quelle: 7(2019), Artikel-ID 24, Seite 1-18
• ISSN Quelle: 2051-5960
• DOI: doi:10.1186/s40478-019-0668-8
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1670044971

Abstract

The introduction of the classification of brain tumours based on their DNA methylation profile has significantly changed the diagnostic approach for cases with ambiguous histology, non-informative or contradictory molecular profiles or for entities where methylation profiling provides useful information for patient risk stratification, for example in medulloblastoma and ependymoma. We present our experience that combines a conventional molecular diagnostic approach with the complementary use of a DNA methylation-based classification tool, for adult brain tumours originating from local as well as national referrals. We report the frequency of IDH mutations in a large cohort of nearly 1550 patients, EGFR amplifications in almost 1900 IDH-wildtype glioblastomas, and histone mutations in 70 adult gliomas. We demonstrate how additional methylation-based classification has changed and improved our diagnostic approach. Of the 325 cases referred for methylome testing, 179 (56%) had a calibrated score of 0.84 and higher and were included in the evaluation. In these 179 samples, the diagnosis was changed in 45 (25%), refined in 86 (48%) and confirmed in 44 cases (25%). In addition, the methylation arrays contain copy number information that usefully complements the methylation profile. For example, EGFR amplification which is 95% concordant with our Real-Time PCR-based copy number assays. We propose here a diagnostic algorithm that integrates histology, conventional molecular tests and methylation arrays.