Methylation array profiling of adult brain tumours: diagnostic outcomes in a large, single centre
| Autor: | Sebastian Brandner, Stefan M. Pfister, Andreas von Deimling, David Capper, Daniel Schrimpf, Zane Jaunmuktane, Monika Dutt, Nirosha Suraweera, Martin Sill, David T.W. Jones |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Oncology Ependymoma lcsh:RC346-429 Cohort Studies 0302 clinical medicine DKFZ classifier H3 K27M Illumina array Medicine Methylation classifier biology Brain Neoplasms Glioma Methylation Adult brain tumours Histone DNA methylation Female IDH1 IDH2 Adult medicine.medical_specialty BRAF Pathology and Forensic Medicine 03 medical and health sciences Cellular and Molecular Neuroscience Internal medicine Biomarkers Tumor Methylation array Molecular diagnostics Humans lcsh:Neurology. Diseases of the nervous system Medulloblastoma business.industry Research Histone mutation DNA Methylation medicine.disease DNA Fingerprinting 030104 developmental biology Brain tumour classification biology.protein Neurology (clinical) Glioblastoma business 030217 neurology & neurosurgery |
| Zdroj: | Acta Neuropathologica Communications Acta Neuropathologica Communications, Vol 7, Iss 1, Pp 1-18 (2019) |
| ISSN: | 2051-5960 |
| DOI: | 10.1186/s40478-019-0668-8 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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