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cIMPACT-NOW Update 9: Recommendations on Utilization of Genome-Wide DNA Methylation Profiling for Central Nervous System Tumor Diagnostics

Aldape, Kenneth; Capper, David; von Deimling, Andreas; Giannini, Caterina; Gilbert, Mark R; Hawkins, Cynthia; Hench, Jürgen; ... Wesseling, Pieter; + view all (2025) cIMPACT-NOW Update 9: Recommendations on Utilization of Genome-Wide DNA Methylation Profiling for Central Nervous System Tumor Diagnostics. Neuro-Oncology Advances , Article vdae228. 10.1093/noajnl/vdae228. Green open access

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Abstract

Genome-wide DNA methylation signatures correlate with and distinguish central nervous system (CNS) tumor types. Since the publication of the initial CNS tumor DNA methylation classifier in 2018, this platform has been increasingly used as a diagnostic tool for CNS tumors, with multiple studies showing the value and utility of DNA methylation – based classification of CNS tumors. A Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) Working Group was therefore convened to describe the current state of the field and to provide advice based on lessons learned to date. Here, we provide recommendations for the use of DNA methylation-based classification in CNS tumor diagnostics, emphasizing attributes and limitations of the modality. We emphasize that methylation classifier is one diagnostic tool to be used alongside previously established diagnostic tools in a fully integrated fashion. In addition, we provide examples of the inclusion of DNA methylation data within the layered diagnostic reporting format endorsed by the World Health Organization (WHO) and the International Collaboration on Cancer Reporting. We emphasize the need for backwards compatibility of future platforms to enable accumulated data to be compatible with new versions of the array. Finally, we outline the specific connections between methylation classes and CNS WHO tumor types to aid in the interpretation of classifier results. It is hoped that this update will assist the neuro-oncology community in the interpretation of DNA methylation classifier results to facilitate the accurate diagnosis of CNS tumors and thereby help guide patient management.

Type: Article
Title: cIMPACT-NOW Update 9: Recommendations on Utilization of Genome-Wide DNA Methylation Profiling for Central Nervous System Tumor Diagnostics
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/noajnl/vdae228
Publisher version: https://doi.org/10.1093/noajnl/vdae228
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: CNS tumors, DNA methylation profiling, molecular classification, neuropathology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10204289
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