Biomarker-based prognostic stratification of young adult glioblastoma

Abstract

// Rui-qi Zhang 1, 2, 4, * , Zhifeng Shi 4, * , Hong Chen 5 , Nellie Yuk-Fei Chung 1, 2 , Zi Yin 1, 2 , Kay Ka-Wai Li 1, 2 , Danny Tat-Ming Chan 3 , Wai Sang Poon 3 , Jinsong Wu 4 , Liangfu Zhou 4 , Aden Ka-yin Chan 1, 2 , Ying Mao 4 , Ho-Keung Ng 1, 2 1 Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China 2 Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong, China 3 Neurosurgery Division, Department of Surgery, Chinese University of Hong Kong, Hong Kong, China 4 Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China 5 Department of Neuropathology, Huashan Hospital, Fudan University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Aden Ka-yin Chan, e-mail: adenchan@cuhk.edu. hk Ying Mao, e-mail: yingmao168@hotmail.com Ho-Keung Ng, e-mail: hkng@cuhk.edu.hk Keywords: glioblastoma, IDH1, BRAF, H3F3A, prognostication Received: June 14, 2015      Accepted: September 25, 2015      Published: October 05, 2015 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 TERT p 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.