Understanding mechanism of genome instability in hereditary breast cancer induced by telomere dysfunction

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08649
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Gunma University
• Principal Investigator: Konishi Akimitsu 群馬大学, 大学院医学系研究科, 講師 (50381877)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: テロメア / 染色体不安定化 / DNA損傷反応 / 細胞周期 / 乳癌

Outline of Final Research Achievements

Breast cancer is currently the most common cancer in women, with hereditary breast cancer accounting for about 10% of the cases. Mutations in the BRCA1 gene, one of the major causative genes in hereditary breast cancer, cause genome instability. Telomeres are localized at the ends of chromosomes to play an important role in genome stabilization. In this study, we focused on telomere function to elucidate the mechanism of genome instability caused by BRCA1 abnormalities.
This study reveals a detailed molecular mechanism by which the BRCA1 complex regulates the ubiquitination of chromatin in the telomere region and represses chromosome end fusion during telomere dysfunction, which leads a genome instability.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

遺伝性乳癌は乳癌の中でも治療に難渋するトリプルネガティブ乳癌に含まれ予後不良であり、BRCA 遺伝子に変異が存在すると70%以上という高率で遺伝性乳癌を発症することから、遺伝性乳癌の病態解明は喫緊の課題の一つである。テロメアによる染色体末端融合は、癌で高率で見られるゲノム不安定化を引き起こす原因であり、本研究で明らかになったBRCA1 複合体による染色体末端融合の分子機構に関する知見は、遺伝性乳癌の病態理解と分子標的治療法の開発につながる。