title: Biomarker-based prognostic stratification 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 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.
authors.affiliation: Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong, China.|Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Rui-Qi
authors.initials: RQ
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Neuropathology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Nellie Yuk-Fei
authors.initials: NY
authors.lastname: Chung
authors.affiliation: Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Kay Ka-Wai
authors.initials: KK
authors.lastname: Li
authors.affiliation: Neurosurgery Division, Department of Surgery, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Danny Tat-Ming
authors.initials: DT
authors.lastname: Chan
authors.affiliation: Neurosurgery Division, Department of Surgery, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Wai Sang
authors.initials: WS
authors.lastname: Poon
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Aden Ka-Yin
authors.initials: AK
authors.lastname: Chan
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.|Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D049451:Nomograms; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: BRAF; H3F3A; IDH1; glioblastoma; prognostication