Clinical utility of whole genome DNA methylation profiling as a primary molecular diagnostic assay for central nervous system tumors – a prospective study and guidelines for clinical testing

Abstract Background Central nervous system (CNS) cancer is the 10 th leading cause of cancer-associated deaths for adults, but in pediatric patients and young adults. The variety complexity histologic subtypes can lead to diagnostic errors. DNA methylation an epigenetic modification that provides a tumor-type specific signature be used diagnosis. Methods We performed prospective study using analysis as primary method 1921 brain tumors. All tumors received pathology diagnosis profiling by whole genome methylation, followed next-generation RNA sequencing. Results were stratified concordance between histopathology, establishing utility. Of 1602 cases with WHO diagnosis, identified mismatch 225 (14%), 78 (5%) did not classify any class, additional 110 (7%) confirmed provided prognostic information. 319 carrying 195 different descriptive diagnoses, definitive 273 (86%) cases, separated them into 55 classes, changed grading 58 (18%) cases. Conclusions robust diagnose CNS tumors, improving accuracy, decreasing errors inconclusive providing subclassification. This framework inclusion molecular test professional guidelines benefits include increased improved patient management, refinements clinical trial design.