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Open Access 01-12-2021 | Oligodendroglioma | Research

Loss of H3K27 trimethylation is frequent in IDH1-R132H but not in non-canonical IDH1/2 mutated and 1p/19q codeleted oligodendroglioma: a Japanese cohort study

Authors: Umma Habiba, Hirokazu Sugino, Roumyana Yordanova, Koki Ise, Zen-ichi Tanei, Yusuke Ishida, Satoshi Tanikawa, Shunsuke Terasaka, Ken-ichi Sato, Yuuta Kamoshima, Masahiko Katoh, Motoo Nagane, Junji Shibahara, Masumi Tsuda, Shinya Tanaka

Published in: Acta Neuropathologica Communications | Issue 1/2021

Abstract

Oligodendrogliomas are defined by mutation in isocitrate dehydrogenase (NADP(+)) (IDH)1/2 genes and chromosome 1p/19q codeletion. World Health Organisation diagnosis endorses testing for 1p/19q codeletion to distinguish IDH mutant (Mut) oligodendrogliomas from astrocytomas because these gliomas require different treatments and they have different outcomes. Several methods have been used to identify 1p/19q status; however, these techniques are not routinely available and require substantial infrastructure investment. Two recent studies reported reduced immunostaining for trimethylation at lysine 27 on histone H3 (H3K27me3) in IDH Mut 1p/19q codeleted oligodendroglioma. However, the specificity of H3K27me3 immunostaining in this setting is controversial. Therefore, we developed an easy-to-implement immunohistochemical surrogate for IDH Mut glioma subclassification and evaluated a validated adult glioma cohort. We screened 145 adult glioma cases, consisting of 45 IDH Mut and 1p/19q codeleted oligodendrogliomas, 30 IDH Mut astrocytomas, 16 IDH wild-type (Wt) astrocytomas, and 54 IDH Wt glioblastomas (GBMs). We compared immunostaining with DNA sequencing and fluorescent in situ hybridization analysis and assessed differences in H3K27me3 staining between oligodendroglial and astrocytic lineages and between IDH1-R132H and non-canonical (non-R132H) IDH1/2 Mut oligodendroglioma. A loss of H3K27me3 was observed in 36/40 (90%) of IDH1-R132H Mut oligodendroglioma. In contrast, loss of H3K27me3 was never seen in IDH1-R132L or IDH2-mutated 1p/19q codeleted oligodendrogliomas. IDH Mut astrocytoma, IDH Wt astrocytoma and GBM showed preserved nuclear staining in 87%, 94%, and 91% of cases, respectively. A high recursive partitioning model predicted probability score (0.9835) indicated that the loss of H3K27me3 is frequent to IDH1-R132H Mut oligodendroglioma. Our results demonstrate H3K27me3 immunohistochemical evaluation to be a cost-effective and reliable method for defining 1p/19q codeletion along with IDH1-R132H and ATRX immunostaining, even in the absence of 1p/19q testing.

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Title: Loss of H3K27 trimethylation is frequent in IDH1-R132H but not in non-canonical IDH1/2 mutated and 1p/19q codeleted oligodendroglioma: a Japanese cohort study
Authors: Umma Habiba
Hirokazu Sugino
Roumyana Yordanova
Koki Ise
Zen-ichi Tanei
Yusuke Ishida
Satoshi Tanikawa
Shunsuke Terasaka
Ken-ichi Sato
Yuuta Kamoshima
Masahiko Katoh
Motoo Nagane
Junji Shibahara
Masumi Tsuda
Shinya Tanaka
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Oligodendroglioma
Glioma
Glioma
Glioma
Astrocytoma
Astrocytoma
Astrocytoma
Glioblastoma
Glioblastoma
Glioblastoma
Published in: Acta Neuropathologica Communications / Issue 1/2021
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-021-01194-7

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Loss of H3K27 trimethylation is frequent in IDH1-R132H but not in non-canonical IDH1/2 mutated and 1p/19q codeleted oligodendroglioma: a Japanese cohort study

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