Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification
Abstract
Abstract Meningiomas in pediatric and adolescent/young adult patients are poorly characterized biologically and clinically, and risk stratification is largely extrapolated from adult tumors. We analyze 293 tumors from patients aged 0–39 years using integrated histopathological and molecular profiling. Youth-onset meningiomas are enriched for NF2 and SMARCE1 alterations and exhibit a gain-dominated copy-number landscape, including recurrent chr17q gain, whereas canonical adult high-risk features, such as chr1p loss, lack prognostic significance. Adult-derived prognostic frameworks, including WHO grade, methylation-based stratification and integrated risk scores, fail to predict progression in patients ≤21 years of age. Tumors segregate into age-enriched epigenetic clusters defined by SMARCE1 , NF2 and BAP1 alterations. Among NF2 -altered tumors, patterns of Merlin inactivation, shaped by germline status and co-occurring copy-number variations, delineate biologically divergent subsets. In patients ≤21 years, extent of resection is the dominant predictor of outcome, while molecular features further refine risk assessment. These findings define pediatric and young adult meningiomas as a distinct molecular entity and support age-adapted risk refinement that integrates molecular features with strong clinical determinants.
Article Details
Authors (48)
Natalie Berghaus
Arnault Tauziède-Espariat
Thomas Hielscher
Dilan Savran
Daniel Schrimpf
Kirsten Göbel
Eric Stutheit-Zhao
Lukas Friedrich
Felix Keller
Fuat Kaan Aras
Filippo Nozzoli
Dominik Sturm
Christine L. White
Simone Schmid
Christian Mawrin
Julia E. Neumann
Till Acker
Rudi Beschorner
Christian Hartmann
Irem Saribiyik
Arda Inan
Ayça Erşen-Danyeli
Mariëtte E. G. Kranendonk
Sybren L. N. Maas
Eelke M. Bos
Eleonora Aronica
Saskia M. Peerdeman
Nikki B. Thuijs
Angelika Mühlebner
Benno Kusters
Wilfred F. A. den Dunnen
Cinzia E. Lavarino
Stéphanie Puget
Jason Chiang
Sonika Dahiya
Melike Pekmezci
Arie Perry
Oluwadamilola Akanji
Miriam Ratliff
Christel Herold-Mende
Sandro M. Krieg
Wolfgang Wick
Stefan M. Pfister
Pieter Wesseling
Andreas von Deimling
Pascale Varlet
Felix Sahm
Philipp Sievers