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In myelodysplastic syndromes (MDS), loss of function of EZH2 is known to contribute to pathogenesis, however the pattern of EZH2 mRNA and protein expression in MDS has not been extensively characterized. Material and methods: A total of 26 patients diagnosed with MDS were analyzed in this study. The relationship between EZH2 expression in patient bone marrow samples, evaluated by RT-PCR and immunoblotting, and patient characteristics were analyzed. The function of truncated EZH2 proteins was examined in vitro. Results: EZH2 expression levels and transcript sizes varied considerably between patients, but there was no relationship with the percentage blast component of patient samples. Cloning and sequencing of amplified RT-PCR fragments demonstrated that patients expressed multiple EZH2 transcripts containing insertions or deletions, with or without frameshift, mainly induced by altered splicing. 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Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-Methylation in myelodysplastic syndrome
http://hdl.handle.net/2237/00027924
http://hdl.handle.net/2237/000279243f3a5c6b-8e51-48c4-9f9e-9e9d638dd24c
名前 / ファイル | ライセンス | アクション |
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Shirahata_Adachi_Mizuho (5.7 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2018-04-19 | |||||
タイトル | ||||||
タイトル | Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-Methylation in myelodysplastic syndrome | |||||
言語 | en | |||||
著者 |
Shirahata-Adachi, Mizuho
× Shirahata-Adachi, Mizuho× Iriyama, Chisako× Tomita, Akihiro× Suzuki, Yasuhiro× Shimada, Kazuyuki× Kiyoi, Hitoshi |
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アクセス権 | ||||||
アクセス権 | open access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
権利 | ||||||
言語 | en | |||||
権利情報 | © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | EZH2 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | H3K27 methyltransferase | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Myelodysplastic syndromes | |||||
抄録 | ||||||
内容記述 | Background: EZH2 (enhancer of zeste homolog 2) is a histone H3K27 methyltransferase involved in the pathogenesis of various hematological malignancies. In myelodysplastic syndromes (MDS), loss of function of EZH2 is known to contribute to pathogenesis, however the pattern of EZH2 mRNA and protein expression in MDS has not been extensively characterized. Material and methods: A total of 26 patients diagnosed with MDS were analyzed in this study. The relationship between EZH2 expression in patient bone marrow samples, evaluated by RT-PCR and immunoblotting, and patient characteristics were analyzed. The function of truncated EZH2 proteins was examined in vitro. Results: EZH2 expression levels and transcript sizes varied considerably between patients, but there was no relationship with the percentage blast component of patient samples. Cloning and sequencing of amplified RT-PCR fragments demonstrated that patients expressed multiple EZH2 transcripts containing insertions or deletions, with or without frameshift, mainly induced by altered splicing. All identified frameshift mutations were found to be 5′ to the functional SET domain, and resulted in truncated protein translation. Altered patterns of EZH2 expression was observed in patients with or without alterations in genes involved with RNA splicing, SRSF2, U2AF1 and SF3B1. Functional analysis in vitro revealed that C-terminally truncated EZH2, lacking the SET domain, may impair the methyltransferase function of wild-type EZH2 in a dominant negative fashion. Conclusion: Our findings suggest that the loss of function of EZH2 induced by aberrant splicing, and/or EZH2 mutations resulting in the production of C-terminally truncated proteins, may be involved in MDS pathogenesis. | |||||
言語 | en | |||||
内容記述タイプ | Abstract | |||||
内容記述 | ||||||
内容記述 | ファイル公開日: 2018/12/01 | |||||
言語 | ja | |||||
内容記述タイプ | Other | |||||
出版者 | ||||||
言語 | en | |||||
出版者 | Elsevier | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
出版タイプ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1016/j.leukres.2017.10.015 | |||||
ISSN | ||||||
収録物識別子タイプ | PISSN | |||||
収録物識別子 | 01452126 | |||||
書誌情報 |
en : Leukemia Research 巻 63, p. 90-97, 発行日 2017-12 |
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著者版フラグ | ||||||
値 | author |