title: The H3.3 K27M mutation results in a poorer prognosis in brainstem gliomas than thalamic gliomas in adults.
abstract: Brainstem and thalamic gliomas are rare, and they are poorly understood in adults. Genetic aberrations that occur in these tumors are still unknown. In this study, we investigated whether thalamic gliomas have different genetic aberrations and clinical outcomes compared with brainstem gliomas in adults. Forty-three glioma samples were selected, including 28 brainstem and 15 thalamic gliomas. The frequency of the K27M mutation in adult midline gliomas was 58.1%. High-grade gliomas in the thalamus were statistically significantly more numerous than brainstem gliomas. Patients with K27M mutant brainstem gliomas had a significantly shorter overall survival than patients with wild-type tumors (P = .020) by Cox regression after adjustment for other independent risk factors. However, there was no statistical tendency toward a poorer overall survival in thalamic gliomas containing the K27M mutation compared with wild-type tumors. The presence of the K27M mutation significantly corresponded with mutations in TP53 in thalamic gliomas. Interestingly, the K27M mutation was mutually exclusive with mutations in IDH1, which was detected only in brainstem gliomas. The microarray data identified 86 differentially expressed genes between brainstem and thalamic gliomas with the K27M mutation. The cyclin-dependent kinase 6 (CDK6) gene, which plays an important role in cancer pathways, was found to be differentially expressed between brainstem and thalamic gliomas with K27M mutations. Although the K27M mutation was frequently observed in adult brainstem and thalamic gliomas, this mutation tended to be associated with a poorer prognosis in brainstem gliomas but not in thalamic gliomas. Brainstem gliomas may present different genetic aberrations from thalamic gliomas. These differences may provide guidance for therapeutic decisions for the treatment of adult brainstem and thalamic gliomas, which may have different molecular targets.
authors: Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: jh79330@163.com.
authors: Jie
authors: J
authors: Feng
authors: Neurosurgery Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: shuyuhao@aliyu.com.
authors: Shuyu
authors: S
authors: Hao
authors: Neurosurgery Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China; Medical Center, School of Medicine, Tsinghua University, Beijing 100084, China. Electronic address: pcctt2010@163.com.
authors: Changcun
authors: C
authors: Pan
authors: Neurosurgery Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: zlzxwy@sina.com.
authors: Yu
authors: Y
authors: Wang
authors: Neurosurgery Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: wuzhen1966@aliyun.com.
authors: Zhen
authors: Z
authors: Wu
authors: Neurosurgery Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: zhangjunting2003@aliyun.com.
authors: Junting
authors: J
authors: Zhang
authors: Pathology Research, Duke University Medical Center, Durham, NC 27701. Electronic address: hai.yan@duke.edu.
authors: Hai
authors: H
authors: Yan
authors: Neurosurgery Department, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address: zhangliweittyy@163.com.
authors: Liwei
authors: L
authors: Zhang
authors: Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China. Electronic address: wanhong96@163.com.
authors: Hong
authors: H
authors: Wan
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020295:Brain Stem Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006657:Histones / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D015996:Survival Rate; D013788:Thalamus / Q000473:pathology*; D055815:Young Adult
chemical_list: D006657:Histones
keywords: Adult; Brainstem; Glioma; H3F3A mutation; Thalamus