MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas

Persistent ID (NDL): info:ndljp/pid/11538607

Material type: 博士論文

Author: Abe, Hideaki

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Publication date: 2020-03-23

Material Format: Digital

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Name of awarding university/degree: 新潟大学,博士(医学)

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Note (General)：: Diffuse midline gliomas (DMGs) show resistance to many chemotherapeutic agents including temozolomide (TMZ). Histone gene mutations in DMGs trigger ep...

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Material Type: 博士論文
Title: MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas
Author/Editor: Abe, Hideaki
Publication Date: 2020-03-23
Publication Date (W3CDTF): 2020-03-23
Alternative Title: H3K27M変異型びまん性正中グリオーマにおけるMGMT発現はテモゾロマイド抵抗性に寄与する
Degree grantor/type: 新潟大学
Date Granted: 2020-03-23
Date Granted (W3CDTF): 2020-03-23
Dissertation Number: 甲第4675号
Degree Type: 博士(医学)
Conferring No. (Dissertation): 甲第4675号
Text Language Code: eng
Subject Heading: MGMT
diffuse midline gliomas
histone H3 mutation
epigenetics
DNA hypomethylation
Note (General): Diffuse midline gliomas (DMGs) show resistance to many chemotherapeutic agents including temozolomide (TMZ). Histone gene mutations in DMGs trigger epigenetic changes including DNA hypomethylation, one of which is a frequent lack ofO6-methyl-guanine-DNA methyltransferase (MGMT) promoter methylation, resulting in increased MGMT expression. We established the NGT16 cell line with HIST1H3B K27Mand ACVR1 G328E gene mutations from a DMG patient and used this cell line and other DMG cell lines with H3F3A gene mutation (SF7761, SF8628, JHH-DIPG1) to analyze MGMT promoter methylation, MGMT protein expression, and response to TMZ. Three out of 4 DMG cell lines (NGT16, SF8628, and JHH-DIPG1) had unmethylated MGMT promoter, increased MGMT expression, and showed resistance to TMZ treatment. SF7761 cells with H3F3A gene mutation showed MGMT promoter methylation, lacked MGMT expression, and sensitivity to TMZ treatment. NGT16 line showed response toALK2 inhibitor K02288 treatment in vitro. We confirmed in vitro that MGMT expression contributes to TMZ resistance in DMG cell lines. There is an urgent need to develop new strategies to treat TMZ-resistant DMGs.
Neurologia medico-chirurgica(Tokyo). 2018, 58(7), 290-295.
新大院博(医)甲第909号
元資料の権利情報 : 【○!C】 2020 Abe, Natsumeda, Okada, Watanabe, Tsukamoto, Kanemaru, Yoshimura, Oishi, Hashizume, Kakita and Fujii. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
開始ページ : 1
終了ページ : 10
DOI: info:doi/10.2176/nmc.ra.2018-0044
https://doi.org/info:doi/10.2176/nmc.ra.2018-0044
Persistent ID (NDL): info:ndljp/pid/11538607
https://dl.ndl.go.jp/pid/11538607
Collection: 障害者向け資料
Collection (Materials For Handicapped People:1): テキストデータ
Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
https://dl.ndl.go.jp/collections/A00014
Acquisition Basis: 博士論文（自動収集）
Date Accepted (W3CDTF): 2020-09-07T06:04:08+09:00
Date Created (W3CDTF): 2020-08-31
Format (IMT): application/pdf
Access Restrictions: 国立国会図書館内限定公開
Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
Availability of remote photoduplication service: 可
Periodical Title (URI): http://hdl.handle.net/10191/00051798
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