Oncotarget

Clinical Research Papers:

Biomarker-based prognostic stratification of young adult glioblastoma

Rui-qi Zhang, Zhifeng Shi, Hong Chen, Nellie Yuk-Fei Chung, Zi Yin, Kay Ka-Wai Li, Danny Tat-Ming Chan, Wai Sang Poon, Jinsong Wu, Liangfu Zhou, Aden Ka-yin Chan, Ying Mao and Ho-Keung Ng _

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Oncotarget. 2016; 7:5030-5041. https://doi.org/10.18632/oncotarget.5456

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Abstract

Rui-qi Zhang1,2,4,*, Zhifeng Shi4,*, Hong Chen5, Nellie Yuk-Fei Chung1,2, Zi Yin1,2, Kay Ka-Wai Li1,2, Danny Tat-Ming Chan3, Wai Sang Poon3, Jinsong Wu4, Liangfu Zhou4, Aden Ka-yin Chan1,2, Ying Mao4, Ho-Keung Ng1,2

1Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China

2Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong, China

3Neurosurgery Division, Department of Surgery, Chinese University of Hong Kong, Hong Kong, China

4Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China

5Department 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 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.


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