Search for the New Molecular Targeted Therapies Based on Genetic Profiles of Ovarian Clear Cell Carcinoma

• Project/Area Number: 25861473
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: The University of Tokyo
• Principal Investigator: UEHARA YURIKO 東京大学, 医学部附属病院, 登録研究医 (50648433)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 卵巣明細胞腺癌 / 染色体コピー数解析 / 遺伝子発現解析 / クラスター解析 / ARID1A / PIK3CA

Outline of Final Research Achievements

Among various histological subtypes of epithelial oarian cancer, ovarian clear cell carcinoma is generally chemoresistant and associated with poor clinical outcome even at an early stage. Therfore, biomarkers to predict the prognosis of clear cell carcinoma and the development of novel molecular tarfeted therapies, on the basis of these biomarkers, are warranted.
In this study, we performed single nucleotide polymorphism analysis with clinical samples of ovarian cancer and evaluated the relationships between chromosomal instability and histological subtypes. Then, we performed microarray gene expression profiling and analyzed three subtypes defined with hierarchical clustering of the gene expression data. We further subclassified the clinical samples of clear cell carcinoma by gene expression profiling, and extracted the gene expression profiles and the signal pathway which might be associated with prognosis and chemoresistance of ovarian clear cell carcinoma.

Research Products

• [Journal Article] 右卵巣腫瘍と術前診断された虫垂粘液嚢胞腺腫の1例 (2016)
  • Author(s): 上原 ゆり子, 石本 慶子, 大野 珠美, 山田 陽子, 勢多 真理子, 五味淵 秀人
  • Journal Title: 東京産科婦人科学会会誌 Volume: 65巻1号 Pages: 32-36
  • Peer Reviewed / Open Access
• [Journal Article] ntegrated copy number and expression analysis identifies profiles of whole-arm chromosomal alterations and subgroups with favorable outcome in ovarian clear cell carcinomas. (2015)
  • Author(s): Uehara Y, Oda K, Ikeda Y, Koso T, Tsuji S, Yamamoto S, Asada K, Sone K, Kurikawa R, Makii C, Hagiwara O, Tanikawa M, Maeda D, Hasegawa K, Nakagawa S, Wada-Hiraike O, Kawana K, Fukayama M, Fujiwara K, Yano T, Osuga Y, Fujii T, Aburatani H.
  • Journal Title: PLoS One Volume: 10 Issue: 6 Pages: e0128066-e0128066
  • DOI: 10.1371/journal.pone.0128066
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Antitumor activity of a combination of dual PI3K/mTOR inhibitor SAR245409 and selective MEK1/2 inhibitor pimasertib in endometrial carcinomas. (2015)
  • Author(s): Inaba K, Oda K, Ikeda Y, Sone K, Miyasaka A, Kashiyama T, Fukuda T, Uehara Y, Arimoto T, Kuramoto H, Wada-Hiraike O, Kawana K, Yano T, Osuga Y, Fujii T.
  • Journal Title: Gynecol Oncol. Volume: 138(2) Pages: 323-331
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] PI3K/mTOR pathway inhibition overcomes radioresistance via suppression of the HIF1-α/VEGF pathway in endometrial cancer. (2015)
  • Author(s): Miyasaka A, Oda K, Ikeda Y, Sone K, Fukuda T, Inaba K, Makii C, Enomoto A, Hosoya N, Tanikawa M, Uehara Y, Arimoto T, Kuramoto H, Wada-Hiraike O, Miyagawa K, Yano T, Kawana K, Osuga Y, Fujii T.
  • Journal Title: Gynecol Oncol. Volume: 138(1) Pages: 174-180
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Anti-tumor activity of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in cultured endometrial carcinoma cells (2014)
  • Author(s): A. Miyasaka, K. Oda, Y. Ikeda, O. Wada-Hiraike, T. Kashiyama, A. Enomoto, N. Hosoya, T. Koso, T. Fukuda, K. Inaaba, K. Sone, Y. Uehara, R. Kurikawa, K. Nagasaka, Y.Matsumoto, T. Arimoto, S. Nakagawa, H. Kuramoto, K. Miyagawa, T. Yano, K. Kawana, Y. Osuga, T. Fujii.
  • Journal Title: BMC Cancer Volume: 14 Issue: 1 Pages: 179-179
  • DOI: 10.1186/1471-2407-14-179
  • Peer Reviewed
• [Presentation] 右卵巣腫瘍と術前診断された虫垂粘液嚢胞腺腫の1例 (2015)
  • Author(s): 上原 ゆり子, 石本 慶子, 大野 珠美, 山田 陽子, 勢多 真理子, 五味淵 秀人
  • Organizer: 第375回東京産科婦人科学会例会
  • Place of Presentation: JA共済ビルカンファレンスホール（東京）
  • Year and Date: 2015-09-19
• [Presentation] 腹腔鏡下子宮全摘術後に炎症反応高値と発熱、腹痛が持続し診断に苦慮した症例 (2015)
  • Author(s): 勢多 真理子, 石本 慶子, 大野 珠美, 上原 ゆり子, 山田 陽子, 五味淵 秀人
  • Organizer: 第55回日本産科婦人科内視鏡学会学術講演会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2015-09-10
• [Presentation] Identification of genetic heterogeneity by whole exome sequencing using cell free DNA from blood samples. (2015)
  • Author(s): Kayo Asada, Katsutoshi Oda, Kengo Gotoh, Reiko Kurikawa, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Yuji Ikeda, Yuriko Uehara, Kenbun Sone, Osamu Hiraike-Wada, Kei Kawana, Tetsu Yano, Yutaka Osuga, Tomoyuki Fujii, Hiroyuki Aburatani
  • Organizer: AACR 106th Annual Meeting 2015
  • Place of Presentation: Philadelphia、USA
  • Year and Date: 2015-04-18
  • Int'l Joint Research
• [Presentation] 卵巣明細胞腺癌における統合的ゲノム・エピゲノム解析 (2014)
  • Author(s): 神尊貴裕、織田克利、上原ゆり子、浅田佳代、池田悠至、宮坂亞希、中川俊介、恩田貴志、平池修、川名敬、大須賀穣、藤井知行
  • Organizer: 第66回日本産科婦人科学会学術講演会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2014-04-18 – 2014-04-20
• [Presentation] Anti-tumor effect of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in endometrial carcinoma cell lines (2014)
  • Author(s): Aki Miyasaka, Katsutoshi Oda, Yuji Ikeda, Osamu Wada-Hiraike, Kenbun Sone, Yuriko Uehara, Yoko Matsumoto, Takahide Arimoto, Shunsuke Nakagawa, Hiroyuki Kuramoto, Tetsu Yano, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii
  • Organizer: 2014 AACR annual meeting
  • Place of Presentation: San Diego, California
  • Year and Date: 2014-04-05 – 2014-04-09
• [Presentation] Comparison of genomic alteration patterns between ovarian clear cell carcinoma and renal cell carcinoma (2013)
  • Author(s): Kayo Asada; Takahiro Koso; Katsutoshi Oda; Yuriko Uehara; Shogo Yamamoto; Kenji Tatsuno; Hiroki Ueda; Reiko Kurikawa; Yuji Ikeda; Osamu Hiraike; Kei Kawana; Tetsu Yano; Yutaka Osuga; Tomoyuki Fujii; Hiroyuki Aburatani.
  • Organizer: AACR Special Conference: Advances in Ovarian Cancer Research: From Concept to Clinic
  • Place of Presentation: Miami, FL, USA
• [Presentation] Comparison of genomic alteration patterns between ovarian clear cell carcinoma and renal cell carcinoma (2013)
  • Author(s): Kayo Asada, Takahiro Koso, Katsutoshi Oda, Yuriko Uehara, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Yuji Ikeda, Osamu Hiraike,Kei Kawana, Tetsu Yano, Tomoyuki Fujii, Hiroyuki Aburatani
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 卵巣明細胞腺癌の統合的ゲノム解析 (2013)
  • Author(s): 神尊 貴裕、織田 克利、上原 ゆり子、浅田 佳代、山本 尚吾、辰野 健二、上田 宏生、池田 悠至、平池 修、川名 敬、矢野 哲、藤井 知行、油谷 浩幸
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Book] がん分子標的治療 Vol.14 No.1 (2016)
  • Author(s): 上原 ゆり子 織田 克利
  • Publisher: メディカルレビュー社