Vulnerability to DNA damage and cancer stemness; analysis in glioblastoma

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Hirosaki University
• Principal Investigator: Akira Kurose 弘前大学, 医学研究科, 教授 (70244910)
• Co-Investigator(Kenkyū-buntansha): 小川 薫 弘前大学, 医学部附属病院, 助教 (10815799) ; 鎌滝 章央 弘前大学, 医学研究科, 助教 (60360004)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: glioblastoma / 核異型 / 幹細胞性 / DNA傷害 / carcinoma / γH2AX / 二本鎖断裂 / 病理診断

Outline of Final Research Achievements

Prevention from DNA damage is considered to correlate with morphological homogeneity of nuclei as well as with stemness and malignancy; correlation of nuclear shape with protection of DNA and malignancy was subjected. A method to compare homogeneity of nuclear shape was established and it correlated significantly with prevention from DNA damage and expression of some stemness markers in glioblastomas. In cholangiocarcinomas, cases with wildtype TP53 showed significant uniformity of nuclear area compared to those with mutant TP53; the former had a tendency showing uniformity of shortest and longest nuclear axes, nuclear perimeter and nuclear shape compared to the latter. These results convince that important correlation between homogeneity of nuclear shape and biological behavior of tumor cells. Homogeneity of nuclear shape can be induced by protection of DNA and represents stemness.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

病理診断や細胞診断は特に腫瘍医学の上で診断上極めて重要な役割を果たしているが，形態診断に最も重要な核異型に関してはその生じる原因が全く解明されていない．本課題は単に核の異型（正常からの隔たり）ではなく，核の均一性がDNA保護と強く関わっている事を想定してそれを証明し，さらにDNA保護作用は幹細胞性とも強く係わることから，核の均一性と腫瘍悪性度に注目してその解明を試み，glioblastomaではその一部を証明し，さらに他の癌腫においてもDNA保護作用を持つとされるTP53遺伝子変異の有無と核形態の均一性を証明した．診断に欠かせない核形態が腫瘍の生物学的態度との相関を指摘したことは意義深い．