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Prevalence and clinicopathological features of H3.3 G34-mutant high-grade gliomas: a retrospective study of 411 consecutive glioma cases in a single institution

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Abstract

A recurrent glycine-to-arginine/valine alteration at codon 34 (G34R/V) within H3F3A, a gene that encodes the replication-independent histone variant H3.3, reportedly occurs exclusively in pediatric glioblastomas. However, the clinicopathological and biological significances of this mutation have not been completely elucidated; especially, no such data exist for tumor samples from Japanese patients. We analyzed 411 consecutive glioma cases representing patients of all ages. Our results demonstrated that 14 patients (3.4%) harbored H3F3A mutations, of which four had G34R mutations and 10 had K27M mutations. G34R-mutant tumors were located in the parietal region in two patients and the basal ganglia in one patient. One patient showed multi-lobular extension similar to the pattern observed in gliomatosis cerebri. Regarding neuroradiological features, intratumoral calcification was evident in two cases and all cases showed no or scarce contrast enhancement on MRI. Histopathologically, the four G34R-mutant cases included three glioblastomas and one astroblastoma. We have also investigated alterations in histone methylation including H3K27me3, H3K9me3, and H3K4me3 in G34R-mutant samples by immunohistochemistry. These results indicate that G34R-mutant tumors are likely to show extensive infiltration and alterations in global histone trimethylation might also play an important role in G34R mutant tumors.

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Acknowledgements

This study was funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan (Grant No. 26462185).

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Authors and Affiliations

  1. Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Fukuoka, 812-8582, Japan

    Koji Yoshimoto, Ryusuke Hatae, Yuhei Sangatsuda, Nobuhiro Hata, Yojiro Akagi, Daisuke Kuga, Murata Hideki & Koji Iihara

  2. Department of Neuropathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Satoshi O. Suzuki & Toru Iwaki

  3. Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Koji Yamashita, Osamu Togao & Akio Hiwatashi

  4. Department of Neurosurgery, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

    Masahiro Mizoguchi

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  1. Koji Yoshimoto
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  2. Ryusuke Hatae
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  3. Yuhei Sangatsuda
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  14. Koji Iihara
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Correspondence to Koji Yoshimoto.

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Yoshimoto, K., Hatae, R., Sangatsuda, Y. et al. Prevalence and clinicopathological features of H3.3 G34-mutant high-grade gliomas: a retrospective study of 411 consecutive glioma cases in a single institution. Brain Tumor Pathol 34, 103–112 (2017). https://doi.org/10.1007/s10014-017-0287-7

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  • DOI: https://doi.org/10.1007/s10014-017-0287-7

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