Analysis of the Growth Mechanism of BAP1-Mutated Cancer Focused on DNA Damage Repair Factors

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Juntendo University (2017-2018); Aichi Cancer Center Research Institute (2015-2016)
• Principal Investigator: Murakami-Tonami Yuko (渡並優子) 順天堂大学, 医学部, 准教授 (70405174)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 合成致死 / 悪性中皮腫 / がん抑制遺伝子 / DNA修復

Outline of Final Research Achievements

The tumor suppressor gene BAP1 is known to be mutated in many cancers, including malignant mesothelioma. When the oncogenic gene is a tumor-suppressor gene, it is generally difficult to develop drugs that activate them. Therefore, we searched for a new molecular target for BAP1 mutation, one of the causative genes of malignant mesothelioma, by focusing on DNA damage response factor using synthetic lethal phenotype. As candidate genes, gene A encoding deubiquitination enzyme and gene B encoding kinase involved in DNA damage repair were obtained.
This suggests that these genes are likely to be novel molecular targets for BAP1-mutant cancers.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果から、BAP1変異がんをはじめとするがん抑制遺伝子変異が原因遺伝子となるがんにおいて、合成致死表現型を用いることで有力な新規分子標的が得られることが明らかとなった。また、BAP1と今回得られた候補遺伝子の関わりについてはこれまで報告がないため、BAP1とこれらの候補遺伝子が合成致死を示す分子機構を明らかとすることで、新たな制御機構を明らかにすることができると考えられる。