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H3 G34-mutant high-grade glioma

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Abstract

H3F3A G34 (H3.3 G34)-mutant high-grade gliomas (HGG) are rare, and newly recognized infiltrating gliomas of the cerebral hemisphere. Here, we report the clinicopathological and molecular characteristics of four H3.3 G34-mutant gliomas in terms of its biological behavior compared to those of glioblastomas (GBMs) and H3 K27M-mutant diffuse midline gliomas (DMGs) of our hospital. The median age of the four patients with H3.3 G34 HGG was 44.5 years (14–66 years). Three patients had tumors in the cerebral hemisphere, whereas one patient had synchronous double tumors in the cerebral hemisphere and posterior fossa. All these tumors were high-grade glioma, but neither microvascular proliferation nor necrosis. They displayed uniform genetic and epigenetic signatures; ATRX-mutant, MGMT promoter-methylated, Olig2-negative, but IDH- and TERT promoter-wildtype. The median survival rate of H3.3 G34-mutant HGGs, IDH-was 23.5 months. In conclusion, H3.3 G34-mutant gliomas were unique HGGs with uniform genetic and epigenetic abnormalities, which suggested a single phylogenic origin. The median survival of H3.3 G34-mutant HGGs was better than those of IDH-wildtype GBMs and H3 K27M-mutant DMGs, but worse than that of IDH-mutant GBM. The tumor-infiltrating area and resectability may be the crucial parameters for the prognosis of the patients.

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Abbreviations

ATRX:

Alpha Thalassemia/Mental Retardation Syndrome X

BWA:

Burrows–Wheeler aligner

CCRT:

Chemotherapy and radiation treatment

CDKN2A:

Cyclin dependent kinase inhibitor 2A

CNV:

Copy number variants

DAXX:

Death domain associated protein

EGFR:

Epidermal growth factor receptor

GATK:

Genome analysis toolkit

BAM:

Binary alignment MAP

GBM:

Glioblastoma

GTR:

Gross total resection

HGG:

High-grade glioma

H3.3:

H3F3A

IDH:

Isocitrate dehydrogenase

KMT:

Lysine methyltransferase

MGMT:

O-6-Methylguanine-DNA methyltransferase

Olig2:

Oligodendrocyte transcription factor 2

pHH3:

Phosphohistone-H3

PNET:

Primitive neuroendocrine tumors

PDGFR:

Platelet derived growth factor receptor alpha

SAM:

Sequence alignment map

SETD2:

SET domain containing 2

SNV:

Single nucleotide variants

TERT:

Telomere reverse transcriptase

WHO:

World Health Organization

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Acknowledgements

This study was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number HI14C1277).

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Authors and Affiliations

  1. Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea

    Ka Young Lim, Jae Kyung Won & Sung-Hye Park

  2. Department of Neurosurgery, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea

    Chul-Kee Park & Seung-Ki Kim

  3. Department of Radiology, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea

    Seung Hong Choi

  4. Department of Internal Medicine, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea

    Taemin Kim

  5. Center for Precision Medicine, Seoul National University Hospital, College of Medicine, Seoul, Republic of Korea

    Jae Kyung Won, Chul-Kee Park, Seung-Ki Kim, Seung Hong Choi, Taemin Kim, Hongseok Yun & Sung-Hye Park

  6. Institute of Neuroscience, Seoul National University College of Medicine, Seoul, Republic of Korea

    Sung-Hye Park

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  1. Ka Young Lim
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Contributions

KYL and S-HP wrote the manuscript. C-KP and S-KK operated, treated the patients and reviewed the clinical data. SHC collected and described the radiological data, TMK treated and described the clinical findings of the patients. KYL and S-HP reviewed the clinicopathological features of the patients. JKW and HY analyzed NGS data and S-HP designed, supervised and edited this clinicopathological research.

Corresponding author

Correspondence to Sung-Hye Park.

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There is no conflict of interest to declare.

Ethical standards

The institutional review board of our hospital approved this study (IRB No: 1906-020-1037) and this study and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. For survival comparison, we obtained the survival data of 52 cases of IDH-mutant GBM, 56 cases of IDH-wildtype GBM, and 13 cases of adult H3 K27M-mutant DMGs, who had been treated at SNUH during 2011 to 2017 (IRB No: 1404-056-572).

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Lim, K.Y., Won, J.K., Park, CK. et al. H3 G34-mutant high-grade glioma. Brain Tumor Pathol 38, 4–13 (2021). https://doi.org/10.1007/s10014-020-00378-8

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  • DOI: https://doi.org/10.1007/s10014-020-00378-8

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