Identification of genomic linkage from ovarian endometriosis to endometrioid carcinoma based on sequential OMICS data analysis

• Project/Area Number: 16K11132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Niigata University
• Principal Investigator: Kashima Katsunori 新潟大学, 医歯学総合病院, 特任教授 (50345500)
• Co-Investigator(Kenkyū-buntansha): 吉原 弘祐 新潟大学, 医歯学系, 研究准教授 (40547535) ; 榎本 隆之 新潟大学, 医歯学系, 教授 (90283754)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 卵巣癌 / 類内膜癌 / 子宮内膜症 / 癌遺伝子 / 卵巣類内膜癌 / 遺伝子変異 / 卵巣類内膜腺癌

Outline of Final Research Achievements

It is well known that ovarian endometrioid carcinoma occurs from endometriosis. Our aim of this study is to clarify the genomic linkage from endometriosis to ovarian endometrioid carcinoma based on sequential genomic analysis. Exome and target-gene sequencing demonstrated that 46.2% and 41.0% of ovarian endometrioid carcinoma harbored KRAS and PIK3CA mutations. On the other hand, around 40% of ovarian endometriosis had KRAS and PIK3CA mutations which were so-called "hot-spot" mutations in cancer. These results suggested that clonal expansion of endometriotic cells with cancer-associated gene mutations might lead to development of ovarian endometrioid carcinoma.

Academic Significance and Societal Importance of the Research Achievements

卵巣類内膜癌が子宮内膜症から発生するメカニズムを解明することは、日本人成人女性の10-20%が罹患している子宮内膜症を外来管理する上で非常に有用な情報になる。さらに、類内膜癌の遺伝子異常に基づいた治療戦略の開発につなげることができるため、本研究の学術的・社会的意義は大きい。

Research Products

• [Presentation] Germline and somatic mutations of homologous recombination associated genes in ovarian cancer (2019)
  • Author(s): Kentaro Sugino, Kosuke Yoshihara, Nozomi Yachida, Manako Yamaguchi, Yutaro Mori, Risa Kudo, Ryo Tamura, Kazuaki Suda, Tatsuya Ishiguro, Sosuke Adachi, Masayuki Sekine, and Takayuki Enomoto
  • Organizer: 第71回日本産科婦人科学会学術講演会
• [Presentation] 卵巣癌組織型別の相同組換え修復異常の評価 (2018)
  • Author(s): 杉野健太郎、吉原弘祐、山口真奈子、谷地田希、森裕太郎、山脇芳、須田一暁、田村亮、石黒竜也、安達聡介、磯部真倫、山口雅幸、関根正幸、榎本隆之、中岡博史、井ノ上逸朗、本山悌一
  • Organizer: 第17回日本婦人科がん分子標的研究会
• [Presentation] Germline and somatic mutations of homologous recombination associated genes in non-serous ovarian cancer (2018)
  • Author(s): Kentaro Sugino, Kosuke Yoshihara, Hirofumi Nakaoka, Nozomi Yachida, Manako Yamaguchi, Yutaro Mori, Risa Kudo, Ryo Tamura, Kazuaki Suda, Tatsuya Ishiguro, Sosuke Adachi, Masanori Isobe, Masayuki Yamaguchi, Masayuki Sekine, Katsunori Kashima, Teiichi Motoyama, Ituro Inoue, and Takayuki Enomoto
  • Organizer: European Society of Gynecological Oncology 2018
  • Int'l Joint Research
• [Presentation] Exome sequencing of endometriosis identifies recurrent somatic mutations in MAPK pathway (2018)
  • Author(s): Kazuaki Suda, Kosuke Yoshihara, Tatsuya Ishiguro, Ryo Tamura, Kaoru Yamawaki, Yutaro Mori, Hiroaki Kase, Ituro Inoue and Takayuki Enomoto
  • Organizer: 第70回日本産科婦人科学会学術講演会