DNA methylation-based classification of central nervous system tumours.
- Capper D
- Jones DTW
- Sill M
- Hovestadt V
- Schrimpf D
- Sturm D
- Koelsche C
- Sahm F
- Chavez L
- Reuss DE
- Kratz A
- Wefers AK
- Huang K
- Pajtler KW
- Schweizer L
- Stichel D
- Olar A
- Engel NW
- Lindenberg K
- Harter PN
- Braczynski AK
- Plate KH
- Dohmen H
- Garvalov BK
- Coras R
- Holsken A
- Hewer E
- Bewerunge-Hudler M
- Schick M
- Fischer R
- Beschorner R
- Schittenhelm J
- Staszewski O
- Wani K
- Varlet P
- Pages M
- Temming P
- Lohmann D
- Selt F
- Witt H
- Milde T
- Witt O
- Aronica E
- Giangaspero F
- Rushing E
- Scheurlen W
- Geisenberger C
- Rodriguez FJ
- Becker A
- Preusser M
- Haberler C
- Bjerkvig R
- Cryan J
- Farrell M
- Deckert M
- Hench J
- Frank S
- Serrano J
- Kannan K
- Tsirigos A
- Bruck W
- Hofer S
- Brehmer S
- Seiz-Rosenhagen M
- Hanggi D
- Hans V
- Rozsnoki S
- Hansford JR
- Kohlhof P
- Kristensen BW
- Lechner M
- Lopes B
- Mawrin C
- Ketter R
- Kulozik A
- Khatib Z
- Heppner F
- Koch A
- Jouvet A
- Keohane C
- Muhleisen H
- Mueller W
- Pohl U
- Prinz M
- Benner A
- Zapatka M
- Gottardo NG
- Driever PH
- Kramm CM
- Muller HL
- Rutkowski S
- von Hoff K
- Fruhwald MC
- Gnekow A
- Fleischhack G
- Tippelt S
- Calaminus G
- Monoranu CM
- Perry A
- Jones C
- Jacques TS
- Radlwimmer B
- Gessi M
- Pietsch T
- Schramm J
- Schackert G
- Westphal M
- Reifenberger G
- Wesseling P
- Weller M
- Collins VP
- Blumcke I
- Bendszus M
- Debus J
- Huang A
- Jabado N
- Northcott PA
- Paulus W
- Gajjar A
- Robinson GW
- Taylor MD
- Jaunmuktane Z
- Ryzhova M
- Platten M
- Unterberg A
- Wick W
- Karajannis MA
- Mittelbronn M
- Acker T
- Hartmann C
- Aldape K
- Schuller U
- Buslei R
- Lichter P
- Kool M
- Herold-Mende C
- Ellison DW
- Hasselblatt M
- Snuderl M
- Brandner S
- Korshunov A
- von Deimling A
- Pfister SM.
Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.