Genome-wide analyses of endometrial endometrioid carcinoma for early detection and personalized medicine.

• Project/Area Number: 26462543
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: SUGIYAMA YUKO 公益財団法人がん研究会, 有明病院 細胞診断部, 部長 (80322634)
• Co-Investigator(Kenkyū-buntansha): 森 誠一 公益財団法人がん研究会, がん研究所 がんゲノム研究部, 主任研究員 (10334814)
• Co-Investigator(Renkei-kenkyūsha): MATSURA Masaaki 公益財団法人がん研究会, がん研究所・がんゲノム研究部, 研究員 (40173794)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 子宮体癌 / 類内膜腺癌 / 発癌 / ゲノム解析 / 原因遺伝子 / 婦人科腫瘍学 / 婦人科腫瘍

Outline of Final Research Achievements

Endometrial endometrioid carcinoma (EEC) has been conventionally considered to be a single disease entity and to be developed from tumorigenic process of hyperplasia carcinoma sequence. Conventional and de novo carcinoma subtypes were then designated as groups1 and 2, respectively. To seek clinical and biological relevance for these two different pathways in EEC development, we performed genomic analyses with group1 and group2 carcinoma. Transcriptional profiling detected activation of estrogen signaling and that of DNA damage pathways in group1 and 2 carcinomas, respectively. Exome sequencing identified POLE mutated, microsatellite instable and copy number high EEAs are predominantly enriched in group2 tumors, while most of carcinomas in group1 exhibit copy number low character. In group1 cases, driver mutations were mostly shared in pairs of concomitant hyperplasia and carcinoma. This study demonstrates biological relevance of the differential tumorigenic process in EECs.

Research Products

• [Presentation] Two distinct tumorigenic processes of endometrial endometrioid adenocarcinoma. (2016)
  • Author(s): Sugiyama Y, Fukui N,.Gotoh O, Hasumi K, Takazawa Y, Noda T, Mori S
  • Organizer: 第75回日本癌学会総会
  • Place of Presentation: 横浜・パシフィコ横浜
  • Year and Date: 2016-10-06
• [Presentation] Genomic analyses reveal two distinct biologic entities of endometrial endometrioid carcinoma. (2016)
  • Author(s): Sugiyama Y, Fukui N,.Gotoh O, Hasumi K, Takazawa Y, Noda T, Mori S
  • Organizer: 2016AACR
  • Place of Presentation: 米国・ニューオリンズ・LA, Emest N. Morial Convention Center
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] Genomic analyses reveal two distinct biologic entities of endometrial endometrioid adenocarcinoma. (2015)
  • Author(s): Sugiyama Yuko, Gotoh Osamu, Hasumi Katsuhiko, Takazawa Yutaka, Noda Tetsuo, Mori Seiichi.
  • Organizer: The 74rd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: Nagoya congress center (Aichi・Nagoya)
  • Year and Date: 2015-10-10
• [Presentation] Two distinct biologic entities of endometrial endometrioid adenocarcinoma. (2014)
  • Author(s): Sugiyama Yuko, Gotoh Osamu, Hasumi Katsuhiko, Takazawa Yutaka, Motoyama Teiichi, Noda Tetsuo, Mori Seiichi.
  • Organizer: The 73rd Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: PACIFICO YOKOHAMA (KANAGAWA・YOKOHAMA)
  • Year and Date: 2014-09-25