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

作者信息

Bennett Julie, Levine Adrian B, Nobre Liana, Negm Logine, Chung Jiil, Fang Karen, Johnson Monique, Komosa Martin, Krumholtz Stacey, Nunes Nuno Miguel, Rana Mansuba, Ryall Scott, Sheth Javal, Siddaway Robert, Bale Tejus A, Bouffet Eric, Cusimano Michael D, Das Sunit, Detsky Jay, Dirks Peter, Karajannis Matthias A, Kongkham Paul, Giantini-Larsen Alexandra, Li Bryan Kincheon, Lim-Fat Mary Jane, Lin Andrew L, Mason Warren P, Miller Alexandra, Perry James R, Sahgal Arjun, Sait Sameer Farouk, Tsang Derek S, Zadeh Gelareh, Laperriere Normand, Nguyen Lananh, Gao Andrew, Keith Julia, Munoz David G, Tabori Uri, Hawkins Cynthia

机构信息

Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.

出版信息

Nat Cancer. 2025 May 7. doi: 10.1038/s43018-025-00962-x.

DOI:10.1038/s43018-025-00962-x
PMID:40335748
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.

摘要

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引用本文的文献

[1]
Central Nervous System Tumors in Adolescents and Young Adults.

Curr Neurol Neurosci Rep. 2025-8-12

本文引用的文献

[1]
CBTRUS Statistical Report: American Brain Tumor Association & NCI Neuro-Oncology Branch Adolescent and Young Adult Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020.

Neuro Oncol. 2024-5-6

[2]
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020.

Neuro Oncol. 2023-10-4

[3]
Dabrafenib plus Trametinib in Pediatric Glioma with V600 Mutations.

N Engl J Med. 2023-9-21

[4]
OpenPBTA: The Open Pediatric Brain Tumor Atlas.

Cell Genom. 2023-5-31

[5]
Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric V600-Mutant Low-Grade Glioma.

J Clin Oncol. 2023-1-20

[6]
CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019.

Neuro Oncol. 2022-10-5

[7]
A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues.

Nat Commun. 2022-8-16

[8]
Multi-institutional study of the frequency, genomic landscape, and outcome of IDH-mutant glioma in pediatrics.

Neuro Oncol. 2023-1-5

[9]
Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial.

Clin Cancer Res. 2022-6-13

[10]
Late-Stage Chemoenzymatic Installation of Hydroxy-Bearing Allyl Moiety on the Indole Ring of Tryptophan-Containing Peptides.

Chemistry. 2022-4-6

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