A population-based analysis of the molecular landscape of glioma in adolescents and young adults reveals insights into gliomagenesis.

Abstract

Gliomas are a major cause of cancer-related deaths in adolescents and young adults (AYAs; ages 15-39 years).

Different molecular alterations drive gliomas in children and adults, leading to distinct biology and clinical consequences, but the implications of pediatric- versus adult-type alterations in AYAs are unknown.

Our population-based analysis of 1,456 clinically and molecularly characterized gliomas in patients aged 0-39 years addresses this gap. Pediatric-type alterations were found in 31% of AYA gliomas and conferred superior outcomes compared to adult-type alterations.

AYA low-grade gliomas with specific RAS-MAPK alterations exhibited senescence, tended to arise in different locations and were associated with superior outcomes compared to gliomas in children, suggesting different cellular origins. Hemispheric IDH-mutant, BRAF p.

V600E and FGFR-altered gliomas were associated with the risk of malignant transformation, having worse outcomes with increased age. These insights into gliomagenesis may provide a rationale for earlier intervention for certain tumors to disrupt the typical behavior, leading to improved outcomes.

COI Statement

Competing interests: The authors declare no competing interests.

References:

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Mupparapu, N., Brewster, L., Ostrom, K. F. & Elshahawi, S. I. Late-stage chemoenzymatic installation of hydroxy-bearing allyl moiety on the indole ring of tryptophan-containing peptides. Chemistry 28, e202104614 (2022).
Ostrom, Q. T. et al. CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2016–2020. Neuro Oncol. 25, iv1–iv99 (2023).

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10.1038/s43018-025-00962-x

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