Back to Search Start Over

H3F3A mutant allele specific imbalance in an aggressive subtype of diffuse midline glioma, H3 K27M-mutant

Authors :
Sachi Maeda
Fumiharu Ohka
Yusuke Okuno
Kosuke Aoki
Kazuya Motomura
Kazuhito Takeuchi
Hironao Kusakari
Nobuyuki Yanagisawa
Shinya Sato
Junya Yamaguchi
Kuniaki Tanahashi
Masaki Hirano
Akira Kato
Hiroyuki Shimizu
Yotaro Kitano
Shintaro Yamazaki
Shinji Yamashita
Hideo Takeshima
Keiko Shinjo
Yutaka Kondo
Toshihiko Wakabayashi
Atsushi Natsume
Source :
Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-12 (2020)
Publication Year :
2020
Publisher :
BMC, 2020.

Abstract

Abstract Diffuse midline glioma, H3 K27M-mutant is a lethal brain tumor located in the thalamus, brain stem, or spinal cord. H3 K27M encoded by the mutation of a histone H3 gene such as H3F3A plays a pivotal role in the tumorigenesis of this type of glioma. Although several studies have revealed comprehensive genetic and epigenetic profiling, the prognostic factors of these tumors have not been identified to date. In various cancers, oncogenic driver genes have been found to exhibit characteristic copy number alterations termed mutant allele specific imbalance (MASI). Here, we showed that several diffuse midline glioma, H3 K27M-mutant exhibited high variant allele frequency (VAF) of the mutated H3F3A gene using droplet digital polymerase chain reaction (ddPCR) assays. Whole-genome sequencing (WGS) revealed that these cases had various copy number alterations that affected the mutant and/or wild-type alleles of the H3F3A gene. We also found that these MASI cases showed a significantly higher Ki-67 index and poorer survival compared with those in the lower VAF cases (P

Details

Language :
English
ISSN :
20515960
Volume :
8
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Acta Neuropathologica Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.6022ac32f68642d68773d237f5291135
Document Type :
article
Full Text :
https://doi.org/10.1186/s40478-020-0882-4