Methylation classifiers: Brain tumors, sarcomas, and what's next

Tumor classification has evolved over the last decades with technical progress contributing much to our current concepts. Among diagnostic hallmarks, novelties were immunostaining, Fluorescence in situ hybridization, Sanger sequencing followed by massive parallel DNA sequencing, and recently, epigenetic analyses have entered the stage. Although each of these techniques was revolutionary and, in some way, also disruptive in certain diagnostic fields, it took years to decades for broad implementation into standard pathological-diagnostic algorithms. In contrast, DNA methylation profiling has been accepted in short time as a game changer with lasting impact on brain tumor classification and with potential for classification of other tumor types. This review provides a brief introduction in DNA methylation-based tumor classification. We present why DNA methylation signatures are attractive diagnostic biomarkers, discuss present achievements and future aims and explain the integration of methylation-based classifiers in diagnostic procedure. Finally, we provide an outlook on the challenges and opportunities associated with DNA methylation-based tumor profiling.