Advances in the classification of pediatric brain tumors through DNA methylation profiling: From research tool to frontline diagnostic. Issue 21 (26th September 2018)

• Record Type: Journal Article
• Authors: Kumar, Rahul; Liu, Anthony P. Y.; Orr, Brent A.; Northcott, Paul A.; Robinson, Giles W.
• Is Part Of: Cancer. Volume 124:Issue 21(2018)
• Page Start: 4168
• Page End: 4180
• Publication Date: 2018-09-26
• Subjects: epigenetics -- methylation -- molecular pathology -- neuro‐oncology -- pediatric central nervous system tumors; Cancer -- Periodicals; Cancer -- Cytopathology -- Periodicals; 616.99405
• DOI: 10.1002/cncr.31583
• Languages: English
• ISSNs: 0008-543X

Abstract

Abstract : Despite significant improvements in pediatric brain tumor therapy and outcome, too many children still die of disease, and too many survivors experience significant sequelae as a result of conventional therapies. The molecular characterization of pediatric brain tumors has afforded tremendous insight into the basic biology and clinical management of these deadly childhood diseases. Genomic, epigenomic, and transcriptional profiling have facilitated the identification of significant heterogeneity among previously uniform disease entities. In particular, DNA methylation profiling has emerged as a robust tool for identifying key disease‐specific subgroups that can exhibit distinct clinical outcomes. These approaches, which also complement classic histologic techniques, can suggest key mechanistic underpinnings of tumorigenesis and open the door for better informed and more tailored therapy. By leveraging the results of large‐scale classifications of disease cohorts, novel driver mutations and pathways can be uncovered, enabling the generation of faithful animal models, promoting targeted drug design, informing developmental biology, and ultimately translating into improved clinical management. In this review, progress in the epigenetic classification of common malignant pediatric brain tumors, namely medulloblastoma, ependymoma, high‐grade glioma, atypical teratoid/rhabdoid tumor, and central nervous system embryonal tumors, will be discussed, and the potential role of DNA methylation profiling as a frontline diagnostic modality will be emphasized. Abstract : Pediatric central nervous system tumors are molecularly and clinically diverse pathologies that demonstrate divergent molecular signatures, prognoses, and responses to treatment. Epigenomic characterization, particularly the use of DNA methylation profiling, has emerged as a powerful and robust tool to inform not only the biology underlying tumorigenesis but also the classification, risk stratification, and ultimate clinical management of these tumors.