Impact of H3.3 K27M Mutation on Prognosis and Survival of Grade IV Spinal Cord Glioma on the Basis of New 2016 World Health Organization Classification of the Central Nervous System

Yi, Seong‐Tae; Choi, Sung Yong; Shin, Dong Ah; Kim, Du Su; Choi, Jung‐Ho; Ha, Yoon; Kh, Kim; Suh, Chang Ok; Chang, Jong Hee; Kim, Se Hoon; Yoon, Do Heum

doi:10.1093/neuros/nyy150

Cited by 69 publications

(77 citation statements)

References 39 publications

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“…Despite this, the median survival was reported to be 20.2 months for those with grade IV histopathology 20. Regardless, the average overall survival for patients in both of these studies ranged from 13.2 to 20.2 months 8 20. The patient presented here lived for 31 months after his surgery, making him one of the longest living patients presented in the literature with a histological GBM and a known H3K27M mutation.…”

Section: Discussionmentioning

confidence: 73%

“…However, Yi et al reported improved survival with H3K27M tumours compared with wild type. Despite this, the median survival was reported to be 20.2 months for those with grade IV histopathology 20. Regardless, the average overall survival for patients in both of these studies ranged from 13.2 to 20.2 months 8 20.…”

Section: Discussionmentioning

confidence: 91%

“…Interestingly, further review of these studies reveals that even fewer of these H3K27M mutants were grade IV by histopathology. For example, Yi et al reported on 25 spinal tumours with H3K27 mutation; however, only 15 of these were grade IV gliomas by histological grade 20. Despite an often lower histological grade, tumours that harbour the H3K27 mutation are clinically aggressive and often behave as high-grade gliomas regardless of histology 21 22…”

Section: Discussionmentioning

confidence: 99%

“…The overall survival reported of those diagnosed with H3K27M-mutant spinal cord diffuse glioma is dismal, with a median survival of 6–16 months reported across the literature,1–3 with the longest reported survival of 20 months 9 20. The low incidence of spinal cord GBM overall has resulted in a lack of clinical trials to establish the best course of treatment and management for this devastating disease.…”

Section: Discussionmentioning

confidence: 99%

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Prolonged survival in a patient with a cervical spine H3K27M-mutant diffuse midline glioma

et al. 2019

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We report a case of prolonged survival in a patient with known cervical intramedullary H3K27M-mutant diffuse midline glioma. A 39-year-old man presented for evaluation with several months of progressive upper extremity pain and weakness. MRI of the cervical spine revealed an intramedullary ring-enhancing lesion centred at C3-C4. Following subtotal surgical resection, a diagnosis of glioblastoma (GBM) was confirmed. Subsequent testing at a later date revealed an H3K27M mutation. He was initially treated with radiation and concomitant and adjuvant temozolomide. He had multiply recurrent disease and was treated with various regimens, including the histone deacetylase inhibitor valproic acid. The patient passed away 31 months (~2.5 years) after diagnosis. Our case is one of few reported adult spinal cord GBMs possessing the H3K27M mutation, and one with the longest reported overall survival in the literature to date.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prolonged survival in a patient with a cervical spine H3K27M-mutant diffuse midline glioma

et al. 2019

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“…For intracranial HGGs, the efficacy of BRAF inhibitors has been reported in laboratory and clinical studies . Although genetic analysis has been performed in several cases of spinal cord HGGs, most reports did not describe the BRAF V600E . Therefore, the frequency of BRAF V600E mutation in spinal cord HGGs remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Spinal cord anaplastic astrocytoma with BRAF V600E mutation: A case report and review of literature

et al. 2020

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A 17‐year‐old female complained of lower extremity pain that progressed to low back pain accompanied by paraparesis. Magnetic resonance imaging revealed a mass in the conus medullaris of the spinal cord at the thoracic spine 11–12 level. The patient underwent resection of the mass. The pathological diagnosis was anaplastic astrocytoma based on the densely proliferating astrocytic tumor cells without necrosis or microvascular proliferation. The patient received chemoradiotherapy with oral temozolomide and a total of 54 Gy of local irradiation, followed by 24 courses of temozolomide as maintenance chemotherapy. The patient survived for 8 years without tumor recurrence following the initial treatment. Genetic analysis of the tumor revealed a BRAF V600E mutation that has not yet been reported in spinal cord high‐grade gliomas (HGGs). In recent years, the molecular therapy targeting the BRAF V600E mutation has been applied in clinical practice for several cancer types. Although the frequency in spinal cord HGGs is uncertain, it is necessary to investigate BRAF V600E mutation as a potential therapeutic target in the future.

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EMX1 functions as a tumor inhibitor in spinal cord glioma through transcriptional suppression of WASF2 and inactivation of the Wnt/β‐catenin axis

et al. 2022

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Background: Gliomas are the most frequent and aggressive cancers in the central nervous system, and spinal cord glioma (SCG) is a rare class of the gliomas. Empty spiracles homobox genes (EMXs) have shown potential tumor suppressing roles in glioma, but the biological function of EMX1 in SCG is unclear. Methods:The EMX1 expression in clinical tissues of patients with SCG was examined. SCG cells were extracted from the tissues, and altered expression of EMX1 was then introduced to examine the role of EMX1 in cell growth and invasiveness in vitro.Xenograft tumors were induced in nude mice for in vivo validation. The targets of EXM1 were predicted via bioinformatic analysis and validated by luciferase and ChIP-qPCR assays. Rescue experiments were conducted to validate the involvements of the downstream molecules.Results: EMX1 was poorly expressed in glioma, which was linked to decreased survival rate of patients according to the bioinformatics prediction. In clinical tissues, EMX1 was poorly expressed in SCG, especially in the high-grade tissues. EMX1 upregulation significantly suppressed growth and metastasis of SCG cells in vitro and in vivo.EMX1 bound to the promoter of WASP family member 2 (WASF2) to suppress its transcription. Restoration of WASF2 blocked the tumor-suppressing effect of EMX1.EMX1 suppressed Wnt/β-catenin signaling activity by inhibiting WASF2. Coronaridine, a Wnt/β-catenin-specific antagonist, blocked SCG cell growth and metastasis induced by WASF2. Conclusion:This study elucidates that EMX1 functions as a tumor inhibitor in SCG by suppressing WASF2-dependent activation of the Wnt/β-catenin axis.

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Impact of H3.3 K27M Mutation on Prognosis and Survival of Grade IV Spinal Cord Glioma on the Basis of New 2016 World Health Organization Classification of the Central Nervous System

Cited by 69 publications

References 39 publications

Prolonged survival in a patient with a cervical spine H3K27M-mutant diffuse midline glioma

Prolonged survival in a patient with a cervical spine H3K27M-mutant diffuse midline glioma

Spinal cord anaplastic astrocytoma with BRAF V600E mutation: A case report and review of literature

EMX1 functions as a tumor inhibitor in spinal cord glioma through transcriptional suppression of WASF2 and inactivation of the Wnt/β‐catenin axis

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