Epigenomic analysis with reprogramming technology in lower grade glioma

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10754
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Kyoto University
• Principal Investigator: Arakawa Yoshiki 京都大学, 医学研究科, 特定講師 (20378649)
• Co-Investigator(Kenkyū-buntansha): Thumkeo Dean 京都大学, 医学研究科, 特定准教授 (40372594) ; 平田 英周 金沢大学, がん進展制御研究所, 准教授 (40761937)
• Co-Investigator(Renkei-kenkyūsha): Yamada Yasuhiro 京都大学, iPS細胞研究所, 教授 (70313872)
• Research Collaborator: Liu Bin ; Fukui Nobuyuki ; Terada Yukinori ; Matsui Yasuzumi ; Makino Yasuhide ; Sumiyoshi Sosuke ; Hattori Etsuko ; Yokogawa Ryuta
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 低悪性度グリオーマ / ダイレクトリプログラミング / エピゲノム異常 / 分化誘導 / 脳腫瘍 / グリオーマ / エピゲノム / iPS

Outline of Final Research Achievements

Although cell lines and spheroid colony lines were established from glioma surgical specimens containing tumor stem cells, cell lines with IDH1R132H could not be established. Introduction of IDH1R132H into human induced pluripotent stem (iPS) cells and neural stem cells derived from iPS cells impaired those cell proliferation. These results suggest that the IDH1R132H impairs cell survival and proliferation, which is a kind of senescence. Although the culture of cells with IDH1R132H were carried out under conditions using various drugs, difficulty of cell growth was identified. Taken together, we confirmed that it was impossible to establish iPS-derived neural stem cells with IDH1R132H expression.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

グリオーマは、未だ根治は困難な疾患である。低悪性度グリオーマの多くは、IDH1/2遺伝子変異が初期の遺伝子異常である。本研究では、IDH1遺伝子変異に伴う腫瘍発生の生物学的意義解明を目指した。その結果、IDH1遺伝子変異伴う細胞老化に似たような現象が神経幹細胞に生じることが、腫瘍発生に関わることを示唆した。