Search about germline genetic predisposition to malignant mesothelioma

• Project/Area Number: 26460689
• 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: Yoshikawa Yoshie 兵庫医科大学, 医学部, 講師 (10566673)
• Co-Investigator(Kenkyū-buntansha): 玉置 知子 (橋本知子 / 玉置 知子(橋本知子)) 兵庫医科大学, 医学部, 名誉教授 (10172868)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 悪性中皮腫 / ゲノム解析 / 体細胞変異 / 生殖細胞系列変異 / 易罹患性 / レアバリアント / 変異 / 機能喪失型バリアント / BAP1 / ゲノム不安定性

Outline of Final Research Achievements

Malignant mesotheliomas are associated to exposure to asbestos and are highly aggressive malignancies in adulthood. To date, only infrequent level of mutations has been reported in this type of tumor. We here detected frequent biallelic deletions, as chromothripsis, in the genes BAP1, SETD2, PBRM1, and SMARCC1 at 3p21 region. We identified germline mutations of BAP1 in Japanese and Caucasian apparently sporadic patients both at frequency of 3%. We also detected missense germline rare variants in SETD2, PBRM1, and SMARCC1; the frequencies differed among ethnicities. These germline mutations may impair gene function and predispose individuals to malignant mesotheliomas.

Research Products

• [Int'l Joint Research] Thoracic Oncology Program/Cancer Center/University of Hawaii(米国)
• [Int'l Joint Research] Department of Cardiothoracic Surgery/Langone Medical Center/New York University(米国)
• [Int'l Joint Research] University of Hawaii/Cancer Center(米国)
• [Int'l Joint Research] New York University/Langone Medical Center(米国)
• [Journal Article] High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma. (2016)
  • Author(s): Yoshikawa Y, Emi M, Hashimoto-Tamaoki T, Ohmuraya M, Sato A, Tsujimura T, Hasegawa S, Nakano T, Nasu M, Pastorino S, Szymiczek A, Bononi A, Tanji M, Pagano I, Gaudino G, Napolitano A, Goparaju C, Pass HI, Yang H, Carbone M.
  • Journal Title: Proc Natl Acad Sci U S A Volume: 113 Issue: 47 Pages: 13432-13437
  • DOI: 10.1073/pnas.1612074113
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] BAP1 mutations in malignant mesotheliomas: a comparison between Japanese and Caucasian patients (2016)
  • Author(s): 吉川良恵、江見充、玉置（橋本）知子
  • Organizer: 第75回日本癌学会
  • Place of Presentation: パシフィコ横浜（横浜, 神奈川）
  • Year and Date: 2016-10-06
• [Presentation] 日本人悪性中皮腫のゲノム解析 (2015)
  • Author(s): 玉置（橋本）知子, 吉川 良恵, 佐藤 智佳, 福岡 和也, 辻村 亨, 中野 孝司
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 京王プラザホテル（東京）
  • Year and Date: 2015-10-14
• [Presentation] 悪性中皮腫と腎細胞がんで高頻度に検出されるBAP1及びPBRM1の変異比較 (2015)
  • Author(s): 吉川 良恵、江見 充、佐藤 鮎子、大搗 泰一郎、辻村 亨、中野 孝司、玉置（橋本） 知子.
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(愛知県、名古屋市）
  • Year and Date: 2015-10-08
• [Presentation] Rare germline variants of transcription regulator genes in malignant mesothe lioma (2014)
  • Author(s): 吉川良恵、大搗泰一郎、久保秀司、佐藤鮎子、辻村亨、江見充、中野孝司、玉置（橋本）知子
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-25 – 2014-09-27