Pediatric and Adolescent/Young Adult High-Grade Gliomas With Adult-Type Molecular Features

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Pediatric Oncology

Background:

• High-grade gliomas (HGGs) in pediatric and adolescent/young adult (AYA) patients are diverse.
• While most HGGs have pediatric molecular features, some present adult-type DNA methylation profiles, impacting diagnosis and treatment.
• Current diagnostic methods may not fully capture this molecular heterogeneity.

Purpose of the Study:

• To investigate the prevalence and characteristics of adult-type molecular profiles in HGGs among patients aged 0-39 years.
• To evaluate the utility of genome-wide DNA methylation profiling in refining diagnoses and identifying therapeutic targets in this age group.

Main Methods:

• Retrospective analysis of 60 HGG, NOS cases (ages 0-39).
• Genome-wide DNA methylation profiling using two independent brain tumor classifiers.
• Copy-number analysis and targeted next-generation sequencing.
• Integration of epigenetic signatures with histopathology for final diagnosis.

Main Results:

• Adult-type molecular profiles were found in 23.3% (14/60) of cases.
• Five of these adult-type cases (35.7%) occurred in patients 18 years or younger.
• Common alterations included NF1 (87.5%), PTEN (62.5%), and TERT promoter mutations (25%).

Conclusions:

• A substantial subset of pediatric and AYA HGGs exhibit adult molecular signatures, challenging age-based diagnostic norms.
• Conventional histopathology and immunohistochemistry have limitations in classifying these HGGs.
• DNA methylation profiling is essential for accurate diagnosis, revealing targetable alterations, and improving patient management.