CNS tumor type prevalence according to age group: An analysis of 21 000 cases confirmed by methylation profiling, with a focus on adolescents and young adults
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Approximately 12 000 adolescents and young adults (ages 15-39, AYAs) are diagnosed with a primary central nervous system (CNS) tumor each year. DNA methylation profiling has transformed CNS tumor classification by refining diagnostic accuracy and identifying biologically distinct subtypes, but its application has not been systematically evaluated in the AYA population. In this study, we examined the spectrum of CNS tumor types across age groups, with a focus on the AYA population. METHODS: We assembled a large dataset of CNS tumor samples with age annotations and methylation profiles matching with high confidence to a CNS tumor type using the NCI/Bethesda classifier. Prevalence of tumor type, methylation class and DNA copy number aberrations were compared across age strata (pediatric, AYA, and adult). RESULTS: The cohort of 21 712 CNS tumors included 5351 tumors from AYAs (25%), which showed a mixed pattern, with tumors typical of childhood (eg, medulloblastoma) as well as those common in older adults (eg, glioblastoma). Several tumor types were specifically enriched in the AYA, including IDH-mutant astrocytoma, pleomorphic xanthoastrocytoma, posterior fossa group B ependymoma, and diffuse hemispheric glioma, H3 G34-mutant, among others. Distinct methylation subclasses of multiple tumor types were observed in the AYA, and patterns of genomic aberrations showed age-specific distributions. CONCLUSION: Large-scale methylation profiling revealed unique classification patterns of CNS tumors in AYAs, with specific tumor types, subclasses, and genomic alterations enriched in this population. These data may serve as a valuable reference resource for better understanding the spectrum of CNS tumors affecting AYA patients.
Source: Neuro-Oncology
Authors: Adriana Fonseca, Leeor Yefet, Omkar Singh, Christopher Dampier, Karen Dazelle, Michelle Lam, Zied Abdullaev, Hye-Jung Chung, Martha Quezado, Mark Raffeld, Jeffrey Gagan, Ina Lee, MacLean Nasrallah, Julie Bennett, Eric Bouffet, Dipak Poria, Pieter Wesseling, Martin van den Bent, Patrick Y Wen, Pascale Varlet, Arnault Tauziède-Espariat, Cristiane M Ida, Gelareh Zadeh, Kenneth Aldape
Institutions: Children's National, Mayo Clinic, National Cancer Institute, Center for Cancer Research, University of Pennsylvania, Hospital for Sick Children, Princess Margaret Cancer Centre, Princess Máxima Center, Amsterdam University Medical Centers, Amsterdam UMC Location Vrije Universiteit Amsterdam, Erasmus MC Cancer Institute, Harvard University, Mass General Brigham, Inserm, Université Paris Cité, Centre Hospitalier Sainte-Anne, Institut de Psychiatrie et Neurosciences de Paris
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Institutes of Health
Award: G9000209169
OpenAlex ID: W7154402143
