Brain tumour diagnostics using a DNA methylation-based classifier as a diagnostic support tool
Priesterbach-Ackley, L P; Boldt, H B; Petersen, J K; Bervoets, N; Scheie, D; Ulhøi, B P; Gardberg, M; Brännström, T; Torp, S H; Aronica, E; Küsters, B; den Dunnen, W F A; de Vos, F Y F L; Wesseling, P; de Leng, W W J; Kristensen, B W
(2020) Neuropathology and Applied Neurobiology, volume 46, issue 5, pp. 478 - 492
(Article)
Abstract
Aims: Methylation profiling (MP) is increasingly incorporated in the diagnostic process of central nervous system (CNS) tumours at our centres in The Netherlands and Scandinavia. We aimed to identify the benefits and challenges of MP as a support tool for CNS tumour diagnostics. Methods: About 502 CNS tumour samples were
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analysed using (850 k) MP. Profiles were matched with the DKFZ/Heidelberg CNS Tumour Classifier. For each case, the final pathological diagnosis was compared to the diagnosis before MP. Results: In 54.4% (273/502) of all analysed cases, the suggested methylation class (calibrated score ≥0.9) corresponded with the initial pathological diagnosis. The diagnosis of 24.5% of these cases (67/273) was more refined after incorporation of the MP result. In 9.8% of cases (49/502), the MP result led to a new diagnosis, resulting in an altered WHO grade in 71.4% of these cases (35/49). In 1% of cases (5/502), the suggested class based on MP was initially disregarded/interpreted as misleading, but in retrospect, the MP result predicted the right diagnosis for three of these cases. In six cases, the suggested class was interpreted as ‘discrepant but noncontributory’. The remaining 33.7% of cases (169/502) had a calibrated score <0.9, including 7.8% (39/502) for which no class indication was given at all (calibrated score <0.3). Conclusions: MP is a powerful tool to confirm and fine-tune the pathological diagnosis of CNS tumours, and to avoid misdiagnoses. However, it is crucial to interpret the results in the context of clinical, radiological, histopathological and other molecular information.
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Keywords: central nervous system tumours, diagnostics, methylation profiling, Clinical Neurology, Neurology, Physiology (medical), Pathology and Forensic Medicine, Histology, Journal Article
ISSN: 0305-1846
Publisher: Wiley-Blackwell
Note: Funding Information: We acknowledge the excellent laboratory work performed by the technicians Rene Sørensen, Anmar Omara Kafel and Tobias Teken Christensen, from the PCR laboratory, at the Department of Pathology, Odense University Hospital, Denmark, as well as by Erwin van der Biezen, Carmen de Voijs and Willem Hoefakker from the molecular laboratory at the Department of Pathology, UMC Utrecht, The Netherlands. Publisher Copyright: © 2020 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
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