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Brain Tumor Pathology
Published in: Brain Tumor Pathology 1/2021

01-01-2021 | Astrocytoma | Original Article

Reduced H3K27me3 levels in diffuse gliomas: association with 1p/19q codeletion and difference from H3K27me3 loss in malignant peripheral nerve sheath tumors

Authors: Keiichiro Kitahama, Shohei Iijima, Ayumi Sumiishi, Akimasa Hayashi, Kiyotaka Nagahama, Kuniaki Saito, Nobuyoshi Sasaki, Keiichi Kobayashi, Saki Shimizu, Motoo Nagane, Junji Shibahara

Published in: Brain Tumor Pathology | Issue 1/2021

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Abstract

Trimethylation of histone H3 at lysine 27 (H3K27me3) acts as a transcriptional repressor of target genes. Recent immunohistochemical studies have reported a loss of H3K27me3 modification in diffuse (especially 1p/19q-codeleted) gliomas. However, we did not observe H3K27me3 loss in diffuse gliomas using routine immunostaining conditions for the detection of H3K27me3 loss in malignant peripheral nerve sheath tumors (MPNSTs). Therefore, we conducted immunohistochemical analysis of surgically resected specimens to understand the differences in the H3K27me3 status in MPNSTs and diffuse gliomas and evaluate the diagnostic utility of H3K27me3 immunohistochemistry. Staining with a standard 1:200 dilution of the C36B11 antibody showed a complete loss of H3K27me3 in 5 out of 11 MPNSTs, whereas most diffuse gliomas (149/151, 98.7%) showed diffuse immunoreactivity. At a 1:2000 antibody dilution, 12.6% (19/151) of the diffuse gliomas showed H3K27me3 loss, which was significantly associated with 1p/19q codeletion (P < 0.001). H3K27me3 loss predicted 1p/19q codeletion in IDH-mutant gliomas with lower sensitivity (56.2%) and higher specificity (100%) than ATRX retention or p53 negative result. In conclusion, reduction in H3K27me3 levels was associated with 1p/19q codeletion in diffuse gliomas; however, the extent of reduction differed from that in MPNSTs, and the results depended on the immunostaining conditions.
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Literature
1.
Baylin SB, Jones PA (2016) Epigenetic determinants of cancer. Cold Spring Harb Perspect Biol 8:a019505CrossRef
2.
Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8:286–298CrossRef
3.
Shen H, Laird PW (2013) Interplay between the cancer genome and epigenome. Cell 153:38–55CrossRef
4.
Lee W, Teckie S, Wiesner T et al (2014) PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. Nat Genet 46:1227–1232CrossRef
5.
Zhang M, Wang Y, Jones S et al (2014) Somatic mutations of SUZ12 in malignant peripheral nerve sheath tumors. Nat Genet 46:1170–1172CrossRef
6.
Prieto-Granada CN, Wiesner T, Messina JL et al (2016) Loss of H3K27me3 expression is a highly sensitive marker for sporadic and radiation-induced MPNST. Am J Surg Pathol 40:479–489CrossRef
7.
Schaefer IM, Fletcher CD, Hornick JL (2016) Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics. Mod Pathol 29:4–13CrossRef
8.
Bender S, Tang Y, Lindroth AM et al (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24:660–672CrossRef
9.
Venneti S, Garimella MT, Sullivan LM et al (2013) Evaluation of histone 3 lysine 27 trimethylation (H3K27me3) and enhancer of Zest 2 (EZH2) in pediatric glial and glioneuronal tumors shows decreased H3K27me3 in H3F3A K27M mutant glioblastomas. Brain Pathol 23:558–564CrossRef
10.
Bayliss J, Mukherjee P, Lu C et al (2016) Lowered H3K27me3 and DNA hypomethylation define poorly prognostic pediatric posterior fossa ependymomas. Sci Transl Med 8:366ra161CrossRef
11.
Panwalkar P, Clark J, Ramaswamy V et al (2017) Immunohistochemical analysis of H3K27me3 demonstrates global reduction in group-A childhood posterior fossa ependymoma and is a powerful predictor of outcome. Acta Neuropathol 134:705–714CrossRef
12.
Hasselblatt M, Johann PD, Kool M, Fruhwald MC (2017) Reduced histone H3 K27 trimethylation is encountered in about 50% of atypical teratoid/rhabdoid tumors (AT/RT) but is not associated with molecular subgroup status and outcome. Acta Neuropathol 134:817–818CrossRef
13.
Kakkar A, Biswas A, Goyal N et al (2016) The Expression of Cyclin D1, VEGF, EZH2, and H3K27me3 in atypical teratoid/rhabdoid tumors of the CNS: a possible role in targeted therapy. Appl Immunohistochem Mol Morphol 24:729–737CrossRef
14.
Katz LM, Hielscher T, Liechty B et al (2018) Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence. Acta Neuropathol 135:955–963CrossRef
15.
Filipski K, Braun Y, Zinke J et al (2019) Lack of H3K27 trimethylation is associated with 1p/19q codeletion in diffuse gliomas. Acta Neuropathol 138:331–334CrossRef
16.
Pekmezci M, Phillips JJ, Dirilenoglu F et al (2020) Loss of H3K27 trimethylation by immunohistochemistry is frequent in oligodendroglioma, IDH-mutant and 1p/19q-codeleted, but is neither a sensitive nor a specific marker. Acta Neuropathol 139:597–600CrossRef
17.
Aihara K, Mukasa A, Nagae G et al (2017) Genetic and epigenetic stability of oligodendrogliomas at recurrence. Acta Neuropathol Commun 5:18CrossRef
18.
Arita H, Yamasaki K, Matsushita Y et al (2016) A combination of TERT promoter mutation and MGMT methylation status predicts clinically relevant subgroups of newly diagnosed glioblastomas. Acta Neuropathol Commun 4:79CrossRef
19.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) (2016) WHO Classification of Tumours of the Central Nervous System. International Agency for Research on Cancer
20.
Takami H, Yoshida A, Fukushima S et al (2015) Revisiting TP53 mutations and immunohistochemistry—a comparative study in 157 diffuse gliomas. Brain Pathol 25:256–265CrossRef
21.
Ikemura M, Shibahara J, Mukasa A et al (2016) Utility of ATRX immunohistochemistry in diagnosis of adult diffuse gliomas. Histopathology 69:260–267CrossRef
22.
Feller C, Felix M, Weiss T et al (2020) Histone epiproteomic profiling distinguishes oligodendroglioma, IDH-mutant and 1p/19q co-deleted from IDH-mutant astrocytoma and reveals less tri-methylation of H3K27 in oligodendrogliomas. Acta Neuropathol 139:211–213CrossRef
23.
Jain SU, Do TJ, Lund PJ et al (2019) PFA ependymoma-associated protein EZHIP inhibits PRC2 activity through a H3 K27M-like mechanism. Nat Commun 10:2146CrossRef
24.
Lu C, Ward PS, Kapoor GS et al (2012) IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 483:474–478CrossRef
Metadata
Title
Reduced H3K27me3 levels in diffuse gliomas: association with 1p/19q codeletion and difference from H3K27me3 loss in malignant peripheral nerve sheath tumors
Authors
Keiichiro Kitahama
Shohei Iijima
Ayumi Sumiishi
Akimasa Hayashi
Kiyotaka Nagahama
Kuniaki Saito
Nobuyoshi Sasaki
Keiichi Kobayashi
Saki Shimizu
Motoo Nagane
Junji Shibahara
Publication date
01-01-2021
Publisher
Springer Singapore
Published in
Brain Tumor Pathology / Issue 1/2021
Print ISSN: 1433-7398
Electronic ISSN: 1861-387X
DOI
https://doi.org/10.1007/s10014-020-00382-y

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