Genomic Biomarkers for Precision Oncology of Salivary Gland Cancer

• Project/Area Number: 18K09340
• 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: Okayama University (2020-2022); The University of Tokyo (2018-2019)
• Principal Investigator: Ando Mizuo 岡山大学, 医歯薬学域, 教授 (60511467)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Salivary gland cancer / Genomic alterations / Precision oncology / 癌ゲノム / 唾液腺癌

Outline of Final Research Achievements

We focused on salivary duct carcinoma (SDC) with pleomorphic adenoma as a precancerous lesion and performed genomic analysis of normal tissue, pleomorphic adenoma, and SDC components in the same case to determine at what stage of malignant transformation the driver mutations occur. The results suggest that inactivation of tumor suppressor genes occurs in the pleomorphic adenoma stage, while copy number aberrations caused by genomic instability are markedly increased, suggesting that these are the drivers of carcinogenesis. These findings contrast with the presence of active mutations in the HRAS and PIK3CA genes in SDCs that are not derived from pleomorphic adenomas, leading to the selection of therapeutic targets.

Academic Significance and Societal Importance of the Research Achievements

唾液腺導管癌は、浸潤性乳管癌に類似した病理組織像を呈する唾液腺悪性腫瘍である。唾液腺導管癌はその由来から、新規癌および多形腺腫由来癌の2種に大別される。唾液腺癌の中で最も悪性度の高い組織型であり、5年生存率は20-30%と報告されている。本研究により得られた知見は、とくに多形腺腫由来癌における重要分子を同定し、患者の治療選択の基準となる治療効果予測因子となることが期待される。

Research Products

• [Journal Article] Identification of novel prognostic and predictive biomarkers in salivary duct carcinoma via comprehensive molecular profiling (2022)
  • Author(s): Kohsaka S, Tada Y, Okami K, et al.
  • Journal Title: NPJ Precis Oncol. Volume: 6 Issue: 1 Pages: 82-82
  • DOI: 10.1038/s41698-022-00324-1
  • Peer Reviewed / Open Access
• [Journal Article] Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma (2022)
  • Author(s): Kawakita Daisuke、Nagao Toshitaka、Takahashi Hideaki、Kano Satoshi、Honma Yoshitaka、Hirai Hideaki、Saigusa Natsuki、Akazawa Kohei、Tani Kaori、Ojiri Hiroya、Tsukahara Kiyoaki、Ozawa Hiroyuki、Okami Kenji、Kondo Takahito、Togashi Takafumi、Fushimi Chihiro、Shimura Tomotaka、Matsuki Takashi、Tada Yuichiro
  • Journal Title: Therapeutic Advances in Medical Oncology Volume: 14 Pages: 175883592211195-175883592211195
  • DOI: 10.1177/17588359221119538
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Role of the EZH2 and H3K27me3 Expression as a Predictor of Clinical Outcomes in Salivary Duct Carcinoma Patients: A Large-Series Study With Emphasis on the Relevance to the Combined Androgen Blockade and HER2-Targeted Therapy (2022)
  • Author(s): Saigusa N, Hirai H, Kohsaka S, et al.
  • Journal Title: Front Oncol Volume: 11 Pages: 779882-779882
  • DOI: 10.3389/fonc.2021.779882
  • Peer Reviewed / Open Access
• [Journal Article] The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma. (2020)
  • Author(s): Hirai H、Tada Y、Nakaguro M、Kawakita D、Sato Y、Shimura T、Tsukahara K、Kano S、Ozawa H、Okami K、Sato Y、Fushimi C、Shimizu A、Okamoto I、Takase S、Okada T、Sato H、Imanishi Y、Otsuka K、Watanabe Y、Sakai A、Ebisumoto K、Togashi T、Ueki Y、Ota H、Saigusa N、Takahashi H、Ando M、Urano M、Hanazawa T、Nagao T
  • Journal Title: Virchows Arch Volume: X Issue: 2 Pages: 291-299
  • DOI: 10.1007/s00428-020-02777-w
  • Peer Reviewed / Open Access / Int'l Joint Research