Exploration of CTCF downstream targets in endometrial cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09634
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: GOTOH Osamu 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 (00634891)
• Co-Investigator(Kenkyū-buntansha): 丸山 玲緒 公益財団法人がん研究会, がん研究所 がんエピゲノムプロジェクト, プロジェクトリーダー (60607985)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: エピゲノム解析 / ゲノム解析 / 婦人科腫瘍学

Outline of Final Research Achievements

CTCF mutations have been reported in several cancer types, including endometrial cancer, and it is known to be a tumor suppressor gene associated with haploinsufficiency. However, its specific role in cancer development has remained unclear. By comparing the methylation status of CTCF/Cohesin binding regions and transcription factor binding regions in CTCF-mutant and wild-type endometrial cancer samples, we found that CTCF-mutant endometrial cancer exhibited hypermethylation in CTCF/Cohesin binding regions as well as in transcription factor binding regions such as ESR1 and FOXA2. This suggests aberrant transcriptional control mediated by hormone receptors with disrupted chromatin structure regulation in endometrial cancer with CTCF mutations.

Free Research Field

がんゲノム学

Academic Significance and Societal Importance of the Research Achievements

染色体高次構造調節因子 CTCF の変異により、類内膜性子宮体癌のがん化が引き起こされる機序を明らかにすることを目的して研究を行った。CTCFの下流因子を、特にエストロゲンシグナルに注目して探索したところ、クロマチン構造制御の異常を伴ったエストロゲンを含む性ホルモン受容体による転写制御の異常を示唆する結果を得た。本研究により子宮体癌の新たなホルモン療法の開発や、染色体高次構造を標的とした治療薬への展開が期待される。