Abstract 3331: Genomic landscape and prognostic indicators in Taiwanese high-grade glioma

Abstract Purpose: High-grade gliomas, including glioblastoma (GBM), are characterized by aggressive phenotypes and a high recurrence rate. Molecular subtyping within high-grade gliomas has advanced diagnostic precision and opened pathways for personalized medicine. IDH mutation status, a critical determinant of high-grade glioma subtypes, reflects distinct patterns in genetic profiles and treatment responses. Given the poor prognosis of high-grade gliomas, there is an urgent need for developing diagnostic tools and therapeutic strategies. Experimental Design: In this VGHTPE cohort, we recruited 192 patients diagnosed with high-grade glioma/GBM between 2009 and 2024. Tumor samples were collected for genomic DNA extraction and analyzed using the FoundationOne CDx test. We assessed the association between genomic alterations and clinical outcomes. Results: Tumor samples from 192 patients (ages 4-82) included 134 IDH-wildtype glioblastomas (69.8%) and 58 IDH-mutant high-grade gliomas (30.2%) based on IDH1/2 status. In the VGHTPE cohort, 21 genes displayed genomic alterations in at least 5% of cases. Over 50% of IDH-wildtype glioblastoma patients exhibited TERT promoter or CDKN2A/B mutations, while over 50% of IDH-mutant glioma patients had TP53 and ATRX mutations. Notably, genes predominantly altered in recurrent tissues were linked to Rap1 signaling. Our analysis showed that IDH1 mutations co-occurred with ATRX and CIC alterations but were mutually exclusive with CDKN2A/B, EGFR, MTAP, and PTEN alterations. Alterations in CDKN2A/B, MTAP, EGFR, PTEN, PIK3CA, and KIT were associated with unfavorable outcomes, whereas patients with IDH1, ATRX, and CIC alterations demonstrated better progression-free survival. Conclusion: This study provides a comprehensive genomic profile of Taiwanese patients with high-grade glioma or GBM, supporting the identification of potential prognostic biomarkers. Citation Format: Chun-Yu Liu, Ji-Lin Chen, Chun-Fu Lin, Jui-To Wang, Wei-Hsin Wang, Cheng-chia Lee, Hsin-Hung Chen, Yi-Wei Chen, Shih-Chieh Lin, Chih-Chun Wu, Chi-Cheng Huang, Sanford P. C. Hsu. Genomic landscape and prognostic indicators in Taiwanese high-grade glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3331.