Detailed analysis of genome structural alteration on 3p21 and clinical application in environment-related cancers.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08982
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Hyogo Medical University
• Principal Investigator: EMI Mitsuru 兵庫医科大学, 医学部, 特別招聘教授 (90221118)
• Co-Investigator(Kenkyū-buntansha): 玉置 知子 (橋本知子) 兵庫医科大学, 医学部, 名誉教授 (10172868) ; 吉川 良恵 兵庫医科大学, 医学部, 講師 (10566673)
• Research Collaborator: YAMAMOTO shingo
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 悪性中皮腫 / 腎細胞がん / 環境癌 / ゲノム構造異常

Outline of Final Research Achievements

We have described that frequent somatic copy number loss throughout the 3p21 region harboring BAP1 and neighbor genes in malignant mesothelioma; many of these minute deletions were not contiguous but rather they alternated with exon segments showing oscillating copy number loss along the 3p21 region. We developed new diagnostic technique, digital MLPA for malignant mesothelioma, that can identify frequent minute biallelic deletions in tumor genome with high accuracy. This technique enabled us to identify frequent minute biallelic deletions in TP53 gene in malignant mesothelioma. In contrast, we found rather large monoallelic deletions encompassing whole short arm of chromosome 3 in renal carcinoma, thus, highlighting these minute oscillating copy number losses as unique features in malignant mesothelioma genome.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

次世代シーケンサーによる塩基配列解析は盛んにされているが、ゲノムコピー数解析は市販のCGHアレイを用いたものが大半で、解像度は数十Kb単位である。我々は、エクソン単位のゲノムコピー数解析が精度高くできる網羅的解析手法を開発し、MMのゲノム変化の特徴を見出した。これまで変異の少ないと考えられてきたMMについて、新規手法を用い、新たなゲノム変化を捉えたことは学術的意義がある。digitalMLPAを用い、体液中のMMを検出する手法を開発できれば、いまだに余命が診断後1年未満であるMMの早期診断を可能にすることができ、社会的意義は大きい。