Identification of driver and thrapeutic resistant pathways by analysing sex-differences in glioblastoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09372
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kochi University
• Principal Investigator: Ueba Tetsuya 高知大学, 教育研究部医療学系臨床医学部門, 教授 (00314203)
• Co-Investigator(Kenkyū-buntansha): 八幡 俊男 高知大学, 教育研究部医療学系臨床医学部門, 助教 (40380323)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膠芽腫 / 染色体工学 / X染色体不活化

Outline of Final Research Achievements

Sex differences have been well identified in incidence and outcome of glioblastoma multiform (GBM), however, the knowledge about the major causes is very limited. X-chromosome inactivation (XCI) is the transcriptional silencing of one X-chromosome in female cells that compensate for the imbalance in gene dosages between XX females and XY meles. In this study, we aimed to elucidate the function of inactivated X-chromosome in sex-difference of GBM using chromosome engineering technology. Selective X chromosome elimination was successfully achieved by multiple chromosome dissections via X-chromosome-targeted genome editing in primary cultured GBM cells with X trisomy and GBM cells with X disomy was isolated by screening. These results suggest that potential induction of chromosomal elimination by chromosomal engineering in GBM cells leads to functional analysis of inactive X chromosome.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

ゲノム編集により不活化X染色体の脱落を誘導することで、この染色体上に存在が想定される性差に関わる因子の同定や機能に関する解析が可能となり得た。染色体工学的手法により新たな膠芽腫の遺伝学的性質や性状の解明が見込まれる。