Brain tumour diagnostics using a DNA methylation‐based classifier as a diagnostic support tool

Abstract

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 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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Affiliated Institutions

• Odense University Hospital DK
• Rigshospitalet DK
• University of Southern Denmark DK
• Copenhagen University Hospital DK
• Utrecht University NL
• Turku University Hospital FI
• University Hospital of Umeå SE
• Aarhus University Hospital DK
• Amsterdam Neuroscience NL
• Amsterdam University Medical Centers NL
• University Medical Center Utrecht NL
• University of Turku FI
• Norwegian University of Science and Technology
• Radboud University Medical Center NL
• University Medical Center Groningen NL
• University of Amsterdam NL
• Radboud University Nijmegen NL

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