Novel treatment strategy against oral potential malignant disorders by suveiling the mutation of the driver gene(s)

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K10044
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Ehime University
• Principal Investigator: Uchida Daisuke 愛媛大学, 医学系研究科, 教授 (20335798)
• Co-Investigator(Kenkyū-buntansha): 栗林 伸行 愛媛大学, 医学系研究科, 助教 (80617332)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: OPMDs / TP53 / OSCC

Outline of Final Research Achievements

We performed mutation analysis of the driver genes in the representative OPMDs, OLP and OLK. Although we detected missense mutation of NOTCH1, PIK3CA, HRAS, and/or nonsense mutation of TP53 in 4 out of 14 cases (28.6%) in OLKs, the mutational cases were not recognized by the histopathological examinations. On the other hands, we detected missense mutation of TP53 in 1 out of 27 cases in OLPs, whereas this case advanced to epithelial dysplasia during the observation period. These results suggested that surveillance of the driver gene mutation could be a novel treatment strategy for the determination of early dissection or stringent observation in OPMDs.

Free Research Field

外科系歯学

Academic Significance and Societal Importance of the Research Achievements

口腔扁平上皮癌(OSCC)は、口腔白板症(OLK)や口腔扁平苔癬(OLP)などの口腔潜在的悪性疾患(OPMDs)が生じ、その後、様々なドライバー遺伝子変異やエピゲノム異常が段階的に蓄積する「multistep carcinogenesis」により発生する。しかしながら、日常臨床で遭遇頻度の高いOLKやOLPでも数%の発癌に過ぎないため、切除か経過観察かの判断は施設ごとに異なり、統一された治療指針がなかった。本研究によりOPMDsの段階でドライバー遺伝子の変異を生じる症例が存在することが明らかとなり、OPMDsの経過観察の厳重化や OSCCの超早期発見・超早期治療につながる可能性が示唆された。