Pediatric spinal high-grade glioma in the pediatric precision oncology registry INFORM: Identification of potential therapeutic targets.

Background: High-grade glioma (HGG) of the spinal cord constitutes rare tumors in the pediatric population. Knowledge of the molecular profile of this pediatric HGG (pedHGG) subgroup is limited and the clinical outcome is poor. Therefore, the aim of this study is to provide more profound investigations of molecular characteristics and clinical features of these tumors.
Methods: Between January 2015 and October 2023, 17 spinal tumors with HGG histology were analyzed by the Individualized Therapy For Relapsed Malignancies in Childhood (INFORM) precision oncology registry. Comprehensive molecular profiling (including next-generation sequencing approaches and DNA methylation analysis) was performed. Clinical data provided by the treating centers were evaluated regarding treatment approaches and outcomes.
Results: Subgroup classification based on DNA methylation analysis revealed molecular HGG subgroups in 12/17 cases, while 2/17 were classified as molecular low-grade glioma (LGG) and 3/17 were not unequivocally classifiable. Typical genetic alterations described in pedHGG usually presenting at other localizations were also present in the counterparts located in the spinal cohort. Alterations that might serve as a promising target for personalized therapy approaches were identified in a subset of tumors.
Conclusion: With this cohort of 12 molecularly confirmed spinal pedHGG cases, we provide a compilation of genomic as well as clinical features of this rare subgroup, contributing to a better understanding and eventually to future treatment approaches.
Competing Interests: A.v.D.: shareholder in Heidelberg Epignostix. C.M.v.T.: advisory board in Alexion, Bayer, Novartis, and Roche. T.M.: research grants from The Brain Tumor Charity, Biomed Valley Discoveries, and Day One Biopharmaceuticals. C.M.K.: advisory board in Boehringer Ingelheim; contracts for clinical trials: Blueprint Rover and Novartis. A.O.v.B: advisory board in Alexion and Novartis. S.M.P: advisory board in BioSkryb; cofounder & shareholder in Heidelberg Epignostix. O.W.: advisory board in Novartis; contracts for clinical trials: Novartis, Bayer, AstraZeneca, Loxo Janssen, Roche, Day One Biopharmaceuticals, and GSK; consulting fees: Roche, BMS, Day One Biopharmaceuticals, Ipsen, and Novartis; receipt of drugs for preclinical testing: BMS, JS Innopharm, Kronos Bio, and ProLynx. D.T.W.J.: advisory board in Day One Biopharmaceuticals; co-founder & shareholder in Heidelberg Epignostix.
(© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)