2022 Fiscal Year Final Research Report

HPV-associated oropharyngeal carcinogenesis by super-enhancer-mediated gene regulation.

Research Project

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Project/Area Number	19K09895
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 56050:Otorhinolaryngology-related
Research Institution	Yokohama City University
Principal Investigator	SANO Daisuke 横浜市立大学, 医学部, 准教授 (10620990)
Co-Investigator(Kenkyū-buntansha)	波多野孝横浜市立大学, 附属病院, 助教 (40807583) 折舘伸彦横浜市立大学, 医学研究科, 教授 (90312355)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	HPV関連中咽頭癌 / ヒトパピローマウイルス / 中咽頭癌 / スーパーエンハンサー / オルガノイド / PDXモデル
Outline of Final Research Achievements	To analyse the relationship between the progression of HPV-related oropharyngeal carcinoma and the tumour microenvironment, an organoid culture method reflecting an environment similar to that of in vivo tissue was used. To establish this culture technique, we attempted to establish organoids using resected specimens from patients with salivary gland cancer and a PDX model. We succeeded in establishing a PDX model/PDXO short-term culture of salivary adenoid cystic carcinoma, a PDX model/PDO/PDXO of salivary duct carcinoma, a PDX model/PDO/PDXO of mucoepidermoid carcinoma and a PDX model of myoepithelial carcinoma. Each model reproduced the original histological features and retained genetic features such as transcriptional profiles, genetic mutations and the presence of fusion genes.
Free Research Field	頭頸部癌
Academic Significance and Societal Importance of the Research Achievements	本研究を介して頭頸部癌研究においても従来の二次元培養に比べてより生体内組織に近い環境を反映することが可能であり，癌周囲の微小環境が解析可能となる三次元培養法によりオルガノイド株樹立が可能であることを示した。このような生体内組織に近い環境を反映可能なモデルが今後の頭頸部癌研究で使用可能となることは，頭頸部癌の発癌機序解明や，頭頸部癌の個別化治療開発に大きく貢献すると考える。