Decoding the DNA methylome of central nervous system tumors: An emerging modality for integrated diagnosis

Abstract The definitive diagnosis and classification of individual cancers are crucial for patient care and cancer research. To achieve a robust diagnosis of central nervous system (CNS) tumors, a genotype‐phenotype integrated diagnostic approach was introduced in recent versions of the World Health Organization classification, followed by the incorporation of a genome‐wide DNA methylome‐based classification. Microarray‐based platforms are widely used to obtain DNA methylome data, and the German Cancer Research Center (Deutsches Krebsforschungszentrum [DKFZ]) has a webtool for a DNA methylation‐based classifier (DKFZ classifier). Integration of DNA methylome will further enhance the precision of CNS tumor classification, especially in diagnostically challenging cases. However, in the clinical application of DNA methylome‐based classification, challenges related to data interpretation persist, in addition to technical caveats, regulations, and limited accessibility. Dimensionality reduction (DMR) can complement integrated diagnosis by visualizing a profile and comparing it with other known samples. Therefore, DNA methylome‐based classification is a highly useful research tool for auxiliary analysis in challenging diagnostic and rare disease cases, and for establishing novel tumor concepts. Decoding the DNA methylome, especially by DMR in addition to DKFZ classifier, emphasizes the capability of grasping the fundamental biological principles that provide new perspectives on CNS tumors.