Molecular mechanism of APOBEC-mediated HPV carcinogenesis and its application as prognosis factor

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16839
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: National Institute of Infectious Diseases (2018); Kanazawa University (2017)
• Principal Investigator: Wakae Kousho 国立感染症研究所, ウイルス第二部, 主任研究官 (70638303)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: APOBEC / HPV / 子宮頸癌 / 遺伝子変異

Outline of Final Research Achievements

We clarified the mechanism how oncogenic host factors, APOBECs, are induced in HPV infected cells. We demonstrated that, differentiation of an HPV16(+) cervical keratinocyte induces APOBEC3A and 3B, as well as mutates host genome (Wakae, Sci. Rep. 2018). In addition, host gene mutations were detected from HPV-associated cancers, including cervical and oropharyngeal cancers, and were correlated with APOBEC3B expression. These results suggested that differentiation of HPV-infected host cells induces APOBECs and mutates their own genome.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

子宮頸がんや中咽頭癌の原因ウイルスであるヒトパピローマウイルス(HPV)が、どのような状況で発癌因子APOBECを発現し、遺伝情報を改変するのか、機序の一端を解明した。ウイルス学的・分子生物学的に重要な発見であると共に、HPV-APOBECによる発現機構を解明する事で、HPV関連癌の新しい予防・治療戦略の創出に貢献すると考えられる。