Pediatric High-Grade Gliomas and Cancer Predisposition Syndromes: A Retrospective Study.

Authors

Selene Cipri, Giada Del Baldo, Emanuele Agolini, Marialetizia Motta, Cecilia Mancini, Claudio Montante, Veronica Capelli, Antonella Cacchione, Mariachiara Lodi, Maria A De Ioris, Sabina Barresi, Isabella Giovannoni, Sabrina Rossi, Evelina Miele, Diana Ferro, Alberto E Tozzi, Angela Gallo, Maria Vinci, Andrea Carai, Rita Alaggio, Antonio Novelli, Marco Tartaglia, Luigi Boccuto, Franco Locatelli, Angela Mastronuzzi

Published in

HGG advances. Pages 100641. Jun 26, 2026. Epub Jun 26, 2026.

Abstract

The relationship between pediatric and adolescent/young adult (AYA) patients with high-grade gliomas (pHGGs) and cancer predisposition syndromes (CPSs) remains insufficiently explored, despite the increasing use of massive parallel sequencing in the diagnostic setting. We retrospectively analyzed sequencing data from 95 pediatric patients diagnosed with high-grade gliomas to investigate the presence of germline variants associated with cancer risk. The presence of somatic variants was also evaluated in 15 cases. In silico and in vitro studies were performed to reclassify one variant of uncertain significance (VUS). We identified 80 variants across the 95 patients, including 17 pathogenic (P), 2 likely pathogenic (LP), 60 VUSs, and 1 likely benign (LB), after reclassification. Notably, 23.7% of the P/LP variants were found in genes associated with CPSs. While the distribution of these variants did not show significant differences across tumor subtypes, the highest proportion of P/LP variants was observed in diffuse midline gliomas. Functional studies led to the reclassification of one LZTR1 variant from VUS to LP. The collected data revealed that 18.9% of patients had P/LP variants; notably, among the 11.6% of patients carrying P/LP variants, there were variants in genes known to be associated with the development of CNS tumors in pediatric and AYA patients, a rate higher than the 10% incidence typically reported in the literature for pediatric central nervous system tumors. This finding emphasizes the value of our comprehensive analysis for germline variants in HGG, suggesting a greater prevalence of CPS in these patients than previously reported.

PMID:
42363591
Bibliographic data and abstract were imported from PubMed on 27 Jun 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.