Discovery of genes responsible for ovarian clear cell carcinoma and gynecological refractory cancers with a cDNA library

Research Project

Project/Area Number	17K16842
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Obstetrics and gynecology
Research Institution	Shinshu University
Principal Investigator	Higuchi Shotaro 信州大学, 学術研究院医学系(医学部附属病院), 助教 (50750098)
Project Period (FY)	2017-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	cDNAライブラリー / 機能的スクリーニング / 卵巣明細胞癌 / 難治性婦人化がん / SEC61B / DVL1 / 難治性婦人科がん / 抗がん剤耐性 / 形質転換 / 卵巣癌 / 難治性婦人科癌 / 機能遺伝子スクリーニング / 婦人科腫瘍
Outline of Final Research Achievements	To discover and identify novel genes that may be deeply involved in the carcinogenesis of ovarian clear-cell carcinoma (OCCC), we created a cDNA library of the OCCC cell line RMG-1 and transfected it into the NIH3TC cells. Then, the cDNAs were identified from the transformed foci with tumor properties. Among the identified genes, SEC61B, DVL1, and C1ORF38 were specifically upregulated in OCCC, suggesting that it is characteristic of OCCC. The transfection of these genes significantly increased the number of transformed foci into NIH3T3. These results indicate that these three genes may be implicated in OCCC carcinogenesis.
Academic Significance and Societal Importance of the Research Achievements	卵巣明細胞癌（OCCC）は日本人に特に多い癌であり、既存の治療に抵抗性であることが大きな問題である。新規治療標的を見出し、新たな治療法を開発していくためにはOCCC発癌の分子メカニズムを解明していく必要がある。本研究で用いた手法は、煩雑であり簡便ではないが、実際に形質転換能を持つ遺伝子を見出す方法であり、有用性は高い。本研究手法では、肺腺癌でEML4-ALK融合遺伝子が見出された実績があり、本研究手法で新たなドライバー遺伝子や融合遺伝子が見出される可能性がある。