Biomarker-based prognostic stratifi cation of young adult glioblastoma

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 identifi ed in over half of the cases. EGFR amplifi cation and TERT p mutation were only detected in 3.7% and 8.4% in young adult glioblastomas, respectively. BRAF -V600E identifi ed 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 identifi ed an aggressive subset of tumors among K27M mutated glioblastomas. Combining BRAF, H3F3A and IDH1 mutations allowed stratifi cation 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 refi ning prognostic classifi cation of glioblastomas.