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

Koji Yoshimoto, Ryusuke Hatae, Yuhei Sangatsuda, Satoshi O. Suzuki, Nobuhiro Hata, Yojiro Akagi, Daisuke Kuga, Murata Hideki, Koji Yamashita, Osamu Togao, Akio Hiwatashi, Toru Iwaki, Masahiro Mizoguchi, Koji Iihara

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13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)103-112
Number of pages10
JournalBrain tumor pathology
Volume34
Issue number3
DOIs
Publication statusPublished - 2017 Jul 1

Keywords

  • G34R/V
  • Glioblastoma
  • H3F3A

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Yoshimoto, K., Hatae, R., Sangatsuda, Y., Suzuki, S. O., Hata, N., Akagi, Y., Kuga, D., Hideki, M., Yamashita, K., Togao, O., Hiwatashi, A., Iwaki, T., Mizoguchi, M., & Iihara, K. (2017). 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 pathology, 34(3), 103-112. https://doi.org/10.1007/s10014-017-0287-7