Abstract
While the predominant elderly and the pediatric glioblastomas have been extensively investigated, young adult glioblastomas were understudied. In this study, we sought to stratify young adult glioblastomas by BRAF, H3F3A and IDH1 mutations and examine the clinical relevance of the biomarkers. In 107 glioblastomas aged from 17 to 35 years, mutually exclusive BRAF-V600E (15%), H3F3A-K27M (15.9%), H3F3A-G34R/V (2.8%) and IDH1-R132H (16.8%) mutations were identified in over half of the cases. EGFR amplification and TERTp mutation were only detected in 3.7% and 8.4% in young adult glioblastomas, respectively. BRAF-V600E identified a clinically favorable subset of glioblastomas with younger age, frequent CDKN2A homozygous deletion, and was more amendable to surgical resection. H3F3A-K27M mutated glioblastomas were tightly associated with midline locations and showed dismal prognosis. IDH1-R132H was associated with older age and favorable outcome. Interestingly, tumors with positive PDGFRA immunohistochemical expression exhibited poorer prognosis and identified an aggressive subset of tumors among K27M mutated glioblastomas. Combining BRAF, H3F3A and IDH1 mutations allowed stratification of young adult glioblastomas into four prognostic subgroups. In summary, our study demonstrates the clinical values of stratifying young adult glioblastomas with BRAF, H3F3A and IDH1 mutations, which has important implications in refining prognostic classification of glioblastomas.
Highlights
Glioblastoma is the commonest and most devastating primary brain cancer [1]
Genomic study in combined series of pediatric and adult glioblastomas further identified age-specific biological subgroups which can be defined by driver events including H3F3A-K27M, H3F3A-G34R/V and Isocitrate dehydrogenase-1 (IDH1) mutations, strongly indicating that glioblastomas are different diseases in different age groups [10, 11]
Our study reveals that BRAF, H3F3A and IDH1 mutations are associated with distinct clinical features and can stratify young adult glioblastomas into prognostic subgroups, which have important clinical implications in refining the prognostic classification of glioblastomas in young adults
Summary
Glioblastoma is the commonest and most devastating primary brain cancer [1]. The disease has a universally fatal prognosis despite aggressive treatment in which over 85% of patients die within two years [2]. While current literature has been only focused in glioblastomas of either children or older patients and in particular, vast majority of adult glioblastomas studied were above 35 years as a result of the skewed distribution towards older age (median age 64 years) [2], the young adult age group was known to have better prognosis [3, 13] but was understudied in the literature In this regards, we investigate a set of subgroup-defining molecular biomarkers in young adult glioblastomas aged from 17 to 35 years and evaluate the prognostic impact of the biomarkers. Our study reveals that BRAF, H3F3A and IDH1 mutations are associated with distinct clinical features and can stratify young adult glioblastomas into prognostic subgroups, which have important clinical implications in refining the prognostic classification of glioblastomas in young adults
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