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

BackgroundGlioblastoma, an aggressive form of high-grade glioma, exhibits variations in the incidence and mortality patterns between populations of different ancestry. However, Hispanic and Latino populations remain largely underrepresented in studies of molecular characterization. Here we characterized the mutagenic landscape of high-grade gliomas within a Chilean population focusing on well characterized genetic variants associated with glioblastoma classification, progression, and prognosis. MethodsWe 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 the most relevant molecular markers such as isocitrate dehydrogenase 1/2 (IDH) mutations, telomerase reverse transcriptase promoter (TERTp) mutations, histone 3 (H3) gene family mutations, TP53 and PTEN mutations, epidermal growth factor receptor (EGFR) gene amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) deletions. Survival analyses were performed to assess the clinical relevance of these markers and their impact on patient prognosis. Additionally, due to our interest in the role of proteostasis and glioblastoma, we investigated possible ERN1 variants in our Chilean cohort. ResultsOur findings mostly align with other international cohorts of non-Latin-American origin, confirming the importance of established molecular markers in glioblastoma. Notably, we identified novel TP53 and PTEN mutations with a predicted damaging effect, expanding the genetic spectrum of alterations in these brain tumors. Furthermore, a lower-than-expected mutation rate in the NF1 gene was observed, emphasizing a distinctive genetic profile of glioblastoma in this Latin American population. Prognostic assessments based on TERT promoter and IDH mutations mirrored previous studies on non-Latino American and European populations. Of note, we identified the germline ERN1 variant rs139229826 in 11% of our patient cohort, a variant previously unreported in glioblastoma patients. ConclusionThis study underscores the importance of conducting glioblastoma research in underrepresented populations, providing insights into the molecular characteristics of high-grade gliomas within a Latin American context. Our findings contribute to the growing body of evidence suggesting molecular diversity across diverse glioblastoma populations, offering a foundation for future international comparative studies.