Initial steps of high-grade serous ovarian carcinoma carcinogenesis

2019 Fiscal Year Annual Research Report

• Project/Area Number: 17K16851
• Research Institution: Keio University
• Principal Investigator: 中村 康平 慶應義塾大学, 医学部(信濃町), 特任助教 (10775802)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 卵巣癌 / 漿液性卵巣癌 / STIC / 全エクソン解析 / ゲノム / 発癌機構

Outline of Annual Research Achievements

卵巣高悪性度漿液性癌（HGSOC）の卵管上皮起源説が注目されている。我々は以前に、癌化に必要な3つの遺伝子異常（p53/KRAS/c-Myc or Akt）を同定し、卵管
采上皮不死化細胞株を用いたin vitro発癌モデルを構築し、発癌初期病変であるSerous tubal intraepithelial carcinoma (STIC) におけるシグナル異常の同定
を行い、 卵管采への排卵時の卵胞液による刺激がHGSOC発癌の初期段階に関与していることが示唆された。2019年度は、申請者はSTICsの有無で卵巣癌の発生母地が異なる可能性があると考え、HGSC症例において全エクソン解析を行い、STICsの有無による遺伝子プロファイルやHRDの有無の比較検討を通して、漿液性卵巣癌発生における分子機構の解明を目的とした。2019年度は全エクソン解析の臨床研究「次世代型統合的がん診断システムの精度向上のために、約1万症例の全エクソン解析を行い、日本人がんゲノムデータベースを構築する研究」を立ち上げ、所属施設以外からの多数の症例を解析できる体制を構築した。また、STIC検索のために、所属施設においてHGSOC症例においては全例で卵管采の全割によるSTIC検索を行える体制を構築した。現在症例登録は順調に進んでおり、今後HGSC症例における全エクソン解析を用いたSTICsの有無による遺伝子プロファイルの比較検討が進めていける状況となった。

Research Products

• [Journal Article] Intratumoral Genomic Heterogeneity May Hinder Precision Medicine Strategies in Patients with Serous Ovarian Carcinoma. (2020)
  • Author(s): Nakamura K, Aimono E, Tanishima S, Imai M, Nagatsuma AK, Hayashi H, Yoshimura Y, Nakayama K, Kyo S, Nishihara H.
  • Journal Title: Diagnostics (Basel). Volume: 10 Pages: -
  • DOI: 10.3390/diagnostics10040200.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Olaparib Monotherapy for BRIP1-Mutated High-Grade Serous Endometrial Cancer (2020)
  • Author(s): Kohei Nakamura, Eriko Aimono, Shigeki Tanishima, Mitsuho Imai, Akiko Kawano Nagatsuma, Hideyuki Hayashi, Yuki Yoshimura, Kentaro Nakayama, Satoru Kyo, and Hiroshi Nishihara,
  • Journal Title: JCO Precision Oncology Volume: - Pages: -
  • DOI: 10.1200/PO.19.00368
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dedifferentiated Endometrial Carcinoma Could be A Target for Immune Checkpoint Inhibitors (Anti PD-1/PD-L1 Antibodies). (2019)
  • Author(s): Ono R, Nakayama K, Nakamura K, Yamashita H, Ishibashi T, Ishikawa M, Minamoto T, Razia S, Ishikawa N, Otsuki Y, Nakayama S, Onuma H, Kurioka H, Kyo S.
  • Journal Title: Int J Mol Sci. Volume: 20 Pages: -
  • DOI: 10.3390/ijms20153744.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinicopathological and biological analysis of PIK3CA mutation and amplification in cervical carcinomas. (2019)
  • Author(s): Razia S, Nakayama K, Nakamura K, Ishibashi T, Ishikawa M, Minamoto T, Iida K, Otsuki Y, Nakayama S, Ishikawa N, Kyo S.
  • Journal Title: Exp Ther Med. Volume: 18 Pages: 2278-2284
  • DOI: 10.3892/etm.2019.7771
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Relationship between Microsatellite Instability, Immune Cells Infiltration, and Expression of Immune Checkpoint Molecules in Ovarian Carcinoma: Immunotherapeutic Strategies for the Future. (2019)
  • Author(s): Yamashita H, Nakayama K, Ishikawa M, Ishibashi T, Nakamura K, Sawada K, Yoshimura Y, Tatsumi N, Kurose S, Minamoto T, Iida K, Razia S, Ishikawa N, Kyo S.
  • Journal Title: Int J Mol Sci. Volume: 20 Pages: -
  • DOI: 10.3390/ijms20205129.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The fallopian tube as origin of ovarian cancer: Change of diagnostic and preventive strategies. (2019)
  • Author(s): Kyo S, Ishikawa N, Nakamura K, Nakayama K.
  • Journal Title: Cancer Med. Volume: 9 Pages: 421-431
  • DOI: 10.1002/cam4.2725.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Sarcopenic Factors May Have No Impact on Outcomes in Ovarian Cancer Patients. (2019)
  • Author(s): Nakayama N, Nakayama K, Nakamura K, Razia S, Kyo S.
  • Journal Title: Diagnostics (Basel). Volume: 9 Pages: -
  • DOI: 10.3390/diagnostics9040206.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients. (2019)
  • Author(s): Ishibashi T, Nakayama K, Razia S, Ishikawa M, Nakamura K, Yamashita H, Dey P, Iida K, Kurioka H, Nakayama S, Otsuki Y, Ishikawa N, Kyo S.
  • Journal Title: Diagnostics (Basel). Volume: 10 Pages: -
  • DOI: 10.3390/diagnostics10010013.
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Book] 臨牀と研究 (2020)
  • Author(s): 中村康平、西原広史
  • Total Pages: 7
  • Publisher: 大道学館出版部
  • ISBN: 0021-4965