Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification

Berghaus, Natalie; Tauziède-Espariat, Arnault; Hielscher, Thomas; Savran, Dilan; Schrimpf, Daniel; Göbel, Kirsten; Stutheit-Zhao, Eric; Friedrich, Lukas; Keller, Felix; Aras, Fuat; Nozzoli, Filippo; Sturm, Dominik; White, Christine; Schmid, Simone; Mawrin, Christian; Neumann, Julia; Acker, Till; Beschorner, Rudi; Hartmann, Christian; Sarıbıyık, Huriye; İnan, MEHMET; Erşen Danyeli, AYÇA; Kranendonk, Mariëtte; Maas, Sybren; Bos, Eelke; Aronica, Eleonora; Peerdeman, Saskia; Thuijs, Nikki; Mühlebner, Angelika; Kusters, Benno; Den Dunnen, Wilfred; Lavarino, Cinzia; Puget, Stéphanie; Chiang, Jason; Dahiya, Sonika; Pekmezci, Melike; Perry, Arie; Akanji, Oluwadamilola; Ratliff, Miriam; Herold-Mende, Christel; Krieg, Sandro; Wick, Wolfgang; Pfister, Stefan; Wesseling, Pieter; Von Deimling, Andreas; Varlet, Pascale; Sahm, Felix; Sievers, Philipp

doi:10.1038/s41467-026-75357-2

Distinct molecular subgroups in pediatric and young-onset meningiomas require age-adapted risk stratification

Berghaus N., Tauziède-Espariat A., Hielscher T., Savran D., Schrimpf D., Göbel K., ...Daha Fazla

NATURE COMMUNICATIONS, cilt.17, sa.1, ss.1-14, 2026 (SCI-Expanded, Scopus)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 17 Sayı: 1
Basım Tarihi: 2026
Doi Numarası: 10.1038/s41467-026-75357-2
Dergi Adı: NATURE COMMUNICATIONS
Derginin Tarandığı İndeksler: Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Health Research Premium Collection (ProQuest), Scopus, Pharma Collection (ProQuest), Technology Collection (ProQuest), Aerospace Database, Science Citation Index Expanded (SCI-EXPANDED), BIOSIS, Chemical Abstracts Core, EMBASE, Geobase, INSPEC, MEDLINE, Directory of Open Access Journals, Zoological Record
Sayfa Sayıları: ss.1-14
Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

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.