DNA methylation based classification of central nervous system tumor [Neurosurgery Wiki]

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====== DNA methylation based classification of central nervous system tumor ======


Capper et al. 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. 

They showed 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, they have designed a free online classifier tool, the use of which does not require any additional onsite data processing. The 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
((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, Hölsken 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, Brück W, Hofer S, Brehmer S, Seiz-Rosenhagen M, Hänggi
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, 
Mühleisen H, Mueller W, Pohl U, Prinz M, Benner A, Zapatka M, Gottardo NG,
Driever PH, Kramm CM, Müller HL, Rutkowski S, von Hoff K, Frühwald 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, Blümcke 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, Schüller 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. DNA methylation-based classification of 
central nervous system tumours. Nature. 2018 Mar 14. doi: 10.1038/nature26000.
[Epub ahead of print] PubMed PMID: 29539639.)).
----
Wenger et al., demonstrated that intra-tumor DNA methylation heterogeneity is a feature of GBM. Although all biopsies were classified as GBM IDH wt/mutated by methylation analysis, the assigned subclass differed in samples from the same patient. The observed heterogeneity within tumors is important to consider for methylation-based biomarkers and future improvements in stratification of GBM patients
((Wenger A, Ferreyra Vega S, Kling T, Olsson Bontell T, Jakola AS, Carén H.
Intra-Tumor DNA Methylation Heterogeneity in Glioblastoma; Implications for DNA
Methylation-Based Classification. Neuro Oncol. 2019 Jan 22. doi:
10.1093/neuonc/noz011. [Epub ahead of print] PubMed PMID: 30668814.
)).