Proteomic analysis in ampullary carcinomas for exploring new therapeutic targets

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04275
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Osaka University (2018-2019); National Cancer Center Japan (2017)
• Principal Investigator: Yachida Shinichi 大阪大学, 医学系研究科, 教授 (20359920)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 十二指腸乳頭部がん / トランスクリプトーム / ChIP-Seq / 希少がん

Outline of Final Research Achievements

Ampullary carcinoma is rare and a highly malignant neoplasm. Therefore, the genomic biology of ampullary carcinomas is currently poorly defined. We have conducted the in-depth analysis of the genomic abnormalities of these carcinomas through an international multi-center collaboration. We identified a characteristic significantly mutated driver gene (ELF3) in these carcinomas by whole-exome sequencing. In this study, we performed transcriptome analysis using these samples and functional analysis of ELF3 by using an immortalized normal epithelial cell line of common bile duct origin. Ampullary carcinomas can be separated into two histological phenotype, intestinal-type or pancreatobilliary-type. The transcriptome analysis demonstrated the different clusters based on the histological phenotype. Functional studies demonstrated that ELF3 silencing in normal human epithelial cells enhances abnormalities of several pathways.

Free Research Field

がんゲノム

Academic Significance and Societal Importance of the Research Achievements

十二指腸乳頭部がんは希少がんであることから、その分子遺伝学的な異常や発がんメカニズムは明らかになっていない。これまでに研究代表者らは日米から希少な凍結組織試料を多数例（172名）収集してきた。本研究ではトランスクリプトーム解析を行い、本疾患の分子遺伝学的な特徴をさらに明らかにした。本研究のような国内外からの検体集積と包括的ゲノム解析は、人種横断的な普遍的なデータが得られ、難治がん・希少がん克服のモデルケースとなることが期待される。