Dual TERT Promoter Mutations in Glioblastoma, IDH-Wildtype: A Case Report with Preclinical Investigations

Telomerase reverse transcriptase promoter ( TERT p) mutations c.-124C > T (C228T) and c.-146C > T (C250T) are the most frequent single-nucleotide variants promoting telomerase activation in glioblastoma. Here, we describe a rare case of glioblastoma IDH -wildtype with dual TERT p mutations. Genomic analyses of multiregional tumor samples revealed co-occurring TERT C228T and C250T mutations across tumor regions, with variable copy number alterations of EGFR and CDKN2A . Notably, only the TERT p C228T mutation was retained in the corresponding patient-derived xenograft, accompanied by more extensive copy number alterations, implying a selective growth advantage for the TERT C228T-harboring subclone during tumor propagation in this case. These findings suggest that dual TERT p mutations may arise through subclonal evolutionary processes in glioblastoma and highlight telomere maintenance as a dynamic, heterogeneous process rather than invariably representing a fixed early oncogenic event.