Characterization of the mutational landscape of high-grade gliomas in a Latin American cohort

We conducted a targeted genomic analysis using next-generation sequencing techniques in 70 Chilean patients with high-grade gliomas from a national single-center referral institution. We focused on relevant molecular markers such as mutations in isocitrate dehydrogenase 1/2 (IDH), telomerase reverse transcriptase promoter (TERTp), histone 3 (H3) gene family, TP53 and PTEN, epidermal growth factor receptor (EGFR) gene amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) deletions. Survival analyses were performed to assess the clinical relevance and their impact on patient prognosis. Additionally, we explored the endoplasmic reticulum stress-related gene ERN1 due to its potential role in high-grade gliomas. This study underscores the importance of glioblastoma research in underrepresented populations, providing insights into high-grade gliomas molecular characteristics within Latin America. Our findings contribute to the growing evidence suggesting molecular diversity across glioblastoma populations, offering a foundation for future international comparative studies. Overall design: We conducted an observational retrospective cohort study, which included 70 patients aged 18 and above with a confirmed diagnosis of high-grade glioma based on the current WHO classification system for CNS tumors at the time. Patients who underwent total or partial resection surgery at the Asenjo Neurosurgery Institute between January 2014 and January 2020 were included in the study. 5 patients who underwent anterior temporal lobectomy for epilepsy treatment were prospectively included in the analysis as non-tumor tissue controls. We utilized the AmpliSeq™ for Illumina tool to create a customized amplicon panel covering specific genomic regions of interest of several neuro-oncology related genes.

本研究针对某国家级单中心转诊机构的70例智利高级别胶质瘤患者，采用二代测序技术开展靶向基因组分析。本研究聚焦于一系列关键分子标志物，包括异柠檬酸脱氢酶1/2（isocitrate dehydrogenase 1/2, IDH）、端粒酶逆转录酶启动子（telomerase reverse transcriptase promoter, TERTp）、组蛋白3（histone 3, H3）基因家族、TP53、PTEN、表皮生长因子受体（epidermal growth factor receptor, EGFR）基因扩增以及细胞周期蛋白依赖性激酶抑制剂2A（cyclin-dependent kinase inhibitor 2A, CDKN2A）缺失。通过生存分析评估上述标志物的临床相关性及其对患者预后的影响。此外，鉴于内质网应激相关基因ERN1在高级别胶质瘤中潜在的调控作用，本研究同时对其展开了探索。本研究凸显了人群代表性不足地区胶质母细胞瘤研究的重要价值，为解析拉丁美洲人群高级别胶质瘤的分子特征提供了新视角。本研究结果进一步佐证了胶质母细胞瘤人群存在分子异质性的学术观点，为后续开展国际多中心对比研究奠定了基础。
研究设计：本研究为回顾性观察性队列研究，纳入2014年1月至2020年1月期间于阿森霍神经外科研究所接受肿瘤全切或部分切除术的70例18岁及以上患者，所有患者均经当时的WHO中枢神经系统肿瘤分类标准确诊为高级别胶质瘤。另前瞻性纳入5例因癫痫接受前颞叶切除术的患者作为非肿瘤组织对照。本研究采用适用于Illumina平台的AmpliSeq™技术构建定制化扩增子测序panel，覆盖多个神经肿瘤相关基因的目标基因组区域。