Functional analysis of salivary gland tumor-associated gene mutations using genetically modified human salivary gland organoids

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16954
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57020:Oral pathobiological science-related
• Research Institution: Showa University
• Principal Investigator: ISHIDA Shoko 昭和大学, 歯学部, 助教 (00882531)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 唾液腺腫瘍 / オルガノイド / TP53 / iPS細胞

Outline of Final Research Achievements

Organoids are three-dimensional structures that mimic specific organs. We had recently succeeded in inducing salivary gland organoids from human iPS cells. In this study, we attempted to reproduce the carcinogenesis process in vitro by generating genetically modified salivary gland organoids with tumor-associated gene mutations of salivary duct carcinoma. The genetically modified human salivary gland organoids showed morphological and protein expression changes like human salivary gland tumors. These data suggested that this mutation may contribute to salivary gland tumorigenesis in patients.

Free Research Field

唾液腺腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究によって、唾液腺導管癌に認められる遺伝子変異が直接的に腫瘍化に寄与している可能性が示唆された。更なる解析により腫瘍発生のメカニズムの解明が期待される。また、本研究で得られた遺伝子改変ヒト唾液腺オルガノイドは、新たな治療標的分子の発見や創薬研究の基盤的技術となり得ることが予想される。本遺伝子改変唾液腺オルガノイドは、疾患メカニズムの解析のみならず、治療法開発においても有用なモデルであると期待される。