2024-03-29T02:29:57Z
https://niigata-u.repo.nii.ac.jp/oai
oai:niigata-u.repo.nii.ac.jp:00034000
2022-12-15T04:04:15Z
453:455
471:561:562
MGMT Expression Contributes to Temozolomide Resistance in H3K27M-Mutant Diffuse Midline Gliomas
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
Abe, Hideaki
【○!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).
MGMT
diffuse midline gliomas
histone H3 mutation
epigenetics
DNA hypomethylation
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
eng
thesis
http://hdl.handle.net/10191/00051798
https://niigata-u.repo.nii.ac.jp/records/34000
info:doi/10.2176/nmc.ra.2018-0044
1
10
13101甲第4675号
博士(医学)
2020-03-23
新潟大学
https://niigata-u.repo.nii.ac.jp/record/34000/files/r1nmk909.pdf
application/pdf
2.3 MB
2020-08-31
https://niigata-u.repo.nii.ac.jp/record/34000/files/r1nmk909_a.pdf
application/pdf
575.9 kB
2020-08-31