Whole-genome analysis of the distribution of tandem duplication, a mechanism of drug resistance in oral cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K17106
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Chiba University
• Principal Investigator: Miyamoto Isao 千葉大学, 医学部附属病院, 助教 (00741836)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: tandem duplication / 次世代シークエンサー / 口腔癌抗癌剤耐性

Outline of Final Research Achievements

We evaluated tandem duplications (TDs) in cetuximab-resistant OSCC cells (SAS-R) and parental OSCC cells (SAS) using NovaSeq 6000 system and DELLY software. We found 941 TD regions in SAS-P and 783 TD regions in SAS-R. Moreover, SAS-R-specific TDs were identified in 10 regions and 17 genes were located in their regions. Among these genes, NLR family pyrin domain containing 7 (NLRP7) was significantly upregulated in cetuximab-resistant OSCC cells of our microarray (GSE114928). Analyzing the relationship between TDs formation and these genes could contribute to a new strategy for overcoming cetuximab resistance.

Free Research Field

口腔癌における分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究のような「系統的に全ゲノム上の遺伝子の発現を制御し，発生，分化，疾患成立，治療抵抗性などに関与しているシステム」の研究が開始されて創薬も絡んだ研究に発展している．本研究も，系統的な複数の遺伝子機能の組み合わせが系統的に疾患を成立させ，各種機能を制御・決定すると考えた点に大きな発想の転換がある．まさに，新規医学・医療技術の開拓を目指した研究であり，臨床応用を見据えた非常に優れた研究である．担癌患者の長期社会復帰などを実現させる可能性があり，社会的意義も大きい．