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H3 K27M encoded by the mutation of a histone H3 gene such as <jats:italic>H3F3A<\/jats:italic> 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 <jats:italic>H3F3A<\/jats:italic> 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 <jats:italic>H3F3A<\/jats:italic> 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 (<jats:italic>P<\/jats:italic>\u00a0&lt;\u20090.05). Our results indicated that the MASI of the <jats:italic>H3F3A K27M<\/jats:italic> mutation was associated with the aggressive phenotype of the diffuse midline glioma, H3 K27M-mutant via upregulation of the H3 K27M mutant protein, resulting in downregulation of H3K27me3 modification.<\/jats:p>","DOI":"10.1186\/s40478-020-0882-4","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:02:58Z","timestamp":1580860978000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["H3F3A mutant allele specific imbalance in an aggressive subtype of diffuse midline glioma, H3 K27M-mutant"],"prefix":"10.1186","volume":"8","author":[{"given":"Sachi","family":"Maeda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiharu","family":"Ohka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Okuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Aoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Motomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Takeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironao","family":"Kusakari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Yanagisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniaki","family":"Tanahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yotaro","family":"Kitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Takeshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiko","family":"Shinjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Wakabayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Natsume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"key":"882_CR1","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/ng.2936","volume":"46","author":"P Buczkowicz","year":"2014","unstructured":"Buczkowicz P, Hoeman C, Rakopoulos P, Pajovic S, Letourneau L, Dzamba M, Morrison A, Lewis P, Bouffet E, Bartels U et al (2014) Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. 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Tumor samples of sequential diffuse midline glioma, H3 K27M-mutant cases that had undergone biopsy from February 2014 to March 2019 were collected intra-operatively upon receiving informed consent from the patients.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8"}}