TY - JOUR
T1 - High-grade gliomas in adolescents and young adults highlight histomolecular differences from their adult and pediatric counterparts
AU - Roux, Alexandre
AU - Pallud, Johan
AU - Saffroy, Raphaël
AU - Edjlali-Goujon, Myriam
AU - Debily, Marie Anne
AU - Boddaert, Nathalie
AU - Sanson, Marc
AU - Puget, Stéphanie
AU - Knafo, Steven
AU - Adam, Clovis
AU - Faillot, Thierry
AU - Cazals-Hatem, Dominique
AU - Mandonnet, Emmanuel
AU - Polivka, Marc
AU - Dorfmüller, Georges
AU - Dauta, Aurélie
AU - Desplanques, Mathilde
AU - Gareton, Albane
AU - Pages, Mélanie
AU - Tauziede-Espariat, Arnault
AU - Grill, Jacques
AU - Bourdeaut, Franck
AU - Doz, François
AU - Dhermain, Frédéric
AU - Mokhtari, Karima
AU - Chretien, Fabrice
AU - Figarella-Branger, Dominique
AU - Varlet, Pascale
N1 - Publisher Copyright:
© The Author(s) 2020.
PY - 2020/8/1
Y1 - 2020/8/1
N2 - 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.
AB - 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.
KW - DNA-methylation analysis
KW - Glioblastoma
KW - Glioma
KW - Integrated diagnosis
KW - Whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85085981661&partnerID=8YFLogxK
U2 - 10.1093/neuonc/noaa024
DO - 10.1093/neuonc/noaa024
M3 - Article
C2 - 32025728
AN - SCOPUS:85085981661
SN - 1522-8517
VL - 22
SP - 1190
EP - 1202
JO - Neuro-Oncology
JF - Neuro-Oncology
IS - 8
ER -