biostudies-literatureStundon JLCCR NIH HHSAlex’s Lemonade Stand Foundation Young Investigator AwardNICHD NIH HHSIntramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer InstituteMarlene Shlomchik Fellowship for Cancer ResearchDivision of Neurosurgery at the Children’s Hospital of PhiladelphiaMatthew Larson FoundationNCI NIH HHSNational Institutes of HealthNIH HHS1331-1342https://www.ebi.ac.uk/biostudies/studies/S-EPMC10326481biostudies-literatureUnknown25(7)<h4>Background</h4>To achieve replicative immortality, most cancers develop a telomere maintenance mechanism, such as reactivation of telomerase or alternative lengthening of telomeres (ALT). There are limited data on the prevalence and clinical significance of ALT in pediatric brain tumors, and ALT-directed therapy is not available.<h4>Methods</h4>We performed C-circle analysis (CCA) on 579 pediatric brain tumors that had corresponding tumor/normal whole genome sequencing through the Open Pediatric Brain Tumor Atlas (OpenPBTA). We detected ALT in 6.9% (n = 40/579) of these tumors and completed additional validation by ultrabright telomeric foci in situ on a subset of these tumors. We used CCA to validate TelomereHunter for computational prediction of ALT status and focus subsequent analysNeuro-oncologyAlternative lengthening of telomeres (ALT) in pediatric high-grade gliomas can occur without ATRX mutation and is enriched in patients with pathogenic germline mismatch repair (MMR) variants.PMC10326481U2C-CA233285HHSN261200800001EK12 HD043245HHSN261200800001CT32 CA0096155T32CA009615-30R03 CA230366R03-CA230362K12HD043245-16U2C CA233285Miller DPStundon JLJin RGuo YLueder MRKim JSanti MKaufman RSLi MStewart DRWaanders AJCorbett RJDiskin SJVaksman ZLopez GResnick ACIjaz HKarras ACole KAGaonkar KSRokita JLStorm PBMacFarland SPfalseAlternative lengthening of telomeres (ALT) in pediatric high-grade gliomas can occur without ATRX mutation and is enriched in patients with pathogenic germline mismatch repair (MMR) variants.<h4>Background</h4>To achieve replicative immortality, most cancers develop a telomere maintenance mechanism, such as reactivation of telomerase or alternative lengthening of telomeres (ALT). There are limited data on the prevalence and clinical significance of ALT in pediatric brain tumors, and ALT-directed therapy is not available.<h4>Methods</h4>We performed C-circle analysis (CCA) on 579 pediatric brain tumors that had corresponding tumor/normal whole genome sequencing through the Open Pediatric Brain Tumor Atlas (OpenPBTA). We detected ALT in 6.9% (n = 40/579) of these tumors and completed additional validation by ultrabright telomeric foci in situ on a subset of these tumors. We used CCA to validate TelomereHunter for computational prediction of ALT status and focus subsequent analys2023-01-01T00:00:00Z2023 Jul2026-07-14T16:49:57.903Z2026-06-21T03:07:26.665ZS-EPMC103264813654155110.1093/neuonc/noac278