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Prognostic role of H3K27M mutation, histone H3K27 methylation status, and EZH2 expression in diffuse spinal cord gliomas

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Abstract

The objective of this study is to clarify clinical significance of the H3F3A K27M mutation (H3K27M) and analyze the correlation between H3K27M, H3K27me3 status, and EZH2 expression and prognosis in spinal cord gliomas. Patients with spinal cord diffuse glioma regardless of World Health Organization (WHO) grade underwent genetic analysis for H3F3A, HIST1H3B, TERT promoter, IDH1/2, and BRAF. H3K27me3 status and EZH2 expression were analyzed through immunohistochemistry. Thereafter, the association between H3K27M, H3K27me3 status, and EZH2 expression and prognosis was retrospectively analyzed using the log-rank test. A total of 26 cases, 5 with WHO grade 4, 9 with grade 3, and 12 with grade 2 glioma, were analyzed. Although WHO grade 2 cases tended to present favorable overall survival, the difference was not statistically significant. H3K27M, which was detected in four grade 4 cases (80%) and three grade 3 cases (33%), was not associated with prognosis among grade 3 and 4 cases. Among WHO grade 2–4 cases, the combination of retained H3K27me3 and negative EZH2 expression was correlated with favorable overall survival (p = 0.03). The combination of H3K27me3 status and EZH2 expression was considered as a potential prognostic marker in WHO grade 2–4 diffuse spinal cord gliomas.

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Abbreviations

DMG:

Diffuse midline glioma

FFPE:

Formalin-fixed paraffin embedded

GBM:

Glioblastoma

H3K27M:

Histone H3K27M mutation

HE:

Hematoxylin and eosin

IHC:

Immunohistochemical staining

KDM6A:

Lysine-specific demethylase 6A

MGMT:

Methylguanine methyltransferase

MRI:

Magnetic resonance imaging

OS:

Overall survival

PRC2:

Polycomb repressive complex 2

TMZ:

Temozolomide

WHO:

World Health Organization

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Acknowledgements

The authors would like to thank Enago (www.enago.jp) for the English review.

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Authors and Affiliations

  1. Department of Neurosurgery, Hokkaido University School of Medicine, North 15 West 7, Kita-ku, Sapporo, 060-8638, Japan

    Yukitomo Ishi, Soichiro Takamiya, Toshitaka Seki, Kazuyoshi Yamazaki & Shigeru Yamaguchi

  2. Department of Neurosurgery, Sapporo Azabu Neurosurgical Hospital, Sapporo, Japan

    Kazutoshi Hida

  3. Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan

    Kanako C. Hatanaka

  4. Department of Cancer Pathology, Hokkaido University School of Medicine, Sapporo, Japan

    Yusuke Ishida, Yoshitaka Oda & Shinya Tanaka

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  1. Yukitomo Ishi
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  2. Soichiro Takamiya
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  4. Kazuyoshi Yamazaki
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Correspondence to Shigeru Yamaguchi.

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Ishi, Y., Takamiya, S., Seki, T. et al. Prognostic role of H3K27M mutation, histone H3K27 methylation status, and EZH2 expression in diffuse spinal cord gliomas. Brain Tumor Pathol 37, 81–88 (2020). https://doi.org/10.1007/s10014-020-00369-9

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  • DOI: https://doi.org/10.1007/s10014-020-00369-9

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