High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts

authors

• Roux Alexandre
• Pallud Johan
• Saffroy Raphaël
• Edjlali-Goujon Myriam
• Debily Marie-Anne
• Boddaert Nathalie
• Sanson Marc
• Puget Stéphanie
• Knafo Steven
• Adam Clovis
• Faillot Thierry
• Cazals-Hatem Dominique
• Mandonnet Emmanuel
• Polivka Marc
• Dorfmüller Georges
• Dauta Aurélie
• Desplanques Mathilde
• Gareton Albane
• Pages Mélanie
• Tauziede-Espariat Arnault
• Grill Jacques
• Bourdeaut Franck
• Doz François
• Dhermain Frédéric
• Mokhtari Karima
• Chretien Fabrice
• Figarella‑branger Dominique
• Varlet Pascale

keywords

• DNA-methylation analysis
• Glioblastoma
• Glioma
• Integrated diagnosis
• Whole exome sequencing

abstract

Background: Considering that pediatric high-grade gliomas (HGGs) are biologically distinct from their adult counterparts, the objective of this study was to define the landscape of HGGs in adolescents and young adults (AYAs). Methods: We performed a multicentric retrospective study of 112 AYAs from adult and pediatric Ile-de-France neurosurgical units, treated between 1998 and 2013 to analyze their clinicoradiological and histomolecular profiles. The inclusion criteria were age between 15 and 25 years, histopathological HGG diagnosis, available clinical data, and preoperative and follow-up MRI. MRI and tumoral samples were centrally reviewed. Immunohistochemistry and complementary molecular techniques such as targeted/next-generation sequencing, whole exome sequencing, and DNA-methylation analyses were performed to achieve an integrated diagnosis according to the 2016 World Health Organization (WHO) classification. Results: Based on 80 documented AYA patients, HGGs constitute heterogeneous clinicopathological and molecular groups, with a predominant representation of pediatric subtypes (histone H3-mutants, 40%) but also adult subtypes (isocitrate dehydrogenase [IDH] mutants, 28%) characterized by the rarity of oligodendrogliomas, IDH mutants, and 1p/19q codeletion and the relative high frequency of “rare adult IDH mutations” (20%). H3G34-mutants (14%) represent the most specific subgroup in AYAs. In the H3K27-mutant subgroup, non-brainstem diffuse midline gliomas are more frequent (66.7%) than diffuse intrinsic pontine gliomas (23.8%), contrary to what is observed in children. We found that WHO grade has no prognostic value, but molecular subgrouping has major prognostic importance. Conclusions: HGGs in AYAs could benefit from a specific classification, driven by molecular subtyping rather than age group. Collaborative efforts are needed from pediatric and adult neuro-oncology teams to improve the management of HGGs in AYAs.

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