Methylation array profiling of adult brain tumours: diagnostic outcomes in a large, single centre

• Published in: Acta neuropathologica communications Vol. 7; no. 1; pp. 24 - 18
• Main Authors: Jaunmuktane, Zane, Capper, David, Jones, David T. W., Schrimpf, Daniel, Sill, Martin, Dutt, Monika, Suraweera, Nirosha, Pfister, Stefan M., von Deimling, Andreas, Brandner, Sebastian
• Format: Journal Article
• Language: English
• Published: London BioMed Central 20.02.2019; BioMed Central Ltd; Nature Publishing Group; BMC
• Subjects: Adult; Algorithms; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; BRAF; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain research; Brain tumors; Classification; Cohort Studies; Criminal investigation; Deoxyribonucleic acid; DNA; DNA Fingerprinting - methods; DNA methylation; DNA Methylation - physiology; Female; Gene mutation; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioma; Gliomas; H3 K27M; Histology; Histone mutation; Humans; IDH1; IDH2; Male; Medical research; Medulloblastoma; Methylation; Methylation array; Morphology; Mutation; Neurology; Neuropathology; Neurosciences; Pathology; Tumors; Molecular diagnostics; IDH1; IDH2; BRAF; Illumina array; Methylation array; Methylation classifier; Histone mutation; Glioma; Adult brain tumours; Brain tumour classification; Ependymoma; H3 K27M; DKFZ classifier
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-019-0668-8

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.