Analysis of genome structural abnormalities of 3p21 in environment-associated cancers

• Project/Area Number: 25460710
• 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, 非常勤講師 (90221118)
• Co-Investigator(Kenkyū-buntansha): TAMAOKI TOMOKO 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, 助教 (10566673)
• Co-Investigator(Renkei-kenkyūsha): YOSHIKAWA YOSHIE 兵庫医科大学, 医学部, 助教 (10566673)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 悪性中皮腫 / 腎細胞がん / 3p21 / BAP1 / biallelic deletion / ゲノム再構成 / SETD2 / ゲノム不安定性 / ゲノムコピー数 / 環境癌 / アレイCGH / MLPA

Outline of Final Research Achievements

In the present study, we sought to analyze environment-associated cancers, i.e., kidney cancer and malignant mesothelioma, for genome structural abnormalities with various advanced genome technologies, such as high-density CGH array, targeted NGS, MLPA, to search for copy number alterations in a chromosome region 3p21 that is suspected to be unstable with our previous knowledge. A simple contiguous large deletion of one allele (LOH) was observed as a characteristic event in kidney cancer. On the contrary, we detected multiple minute genome homozygous deletions in 20/33 tumors in malignant mesotheliomas. Those minute deletions were clustered in 47-48 Mb centered by SETD2 and 52-53 Mb region centered by BAP1. Those tumors presented with homozygous deletion of average of 4.7 genes. Therefore, unlike kidney cancer, key-events in mesothelioma development may associated with multiple minute copy number loss resulted by synchronous fragmentation of 3p21 and aberrant repair.

Research Products

• [Int'l Joint Research] University of Hawaii/Cancer Center/Thoracic Oncology Program(米国)
• [Int'l Joint Research] New York University/Langone Medical Center/Department of Cardiothoracic Surgery(米国)
• [Journal Article] Frequent genomic rearrangements of BRCA1 associated protein-1 (BAP1) gene in Japanese malignant mesothelioma-characterization of deletions at exon level. (2015)
  • Author(s): Emi M et al
  • Journal Title: J Hum Genet Volume: 60 Issue: 10 Pages: 647-649
  • DOI: 10.1038/jhg.2015.91
  • Peer Reviewed
• [Journal Article] High Incidence of Somatic BAP1 Alterations in Sporadic Malignant Mesothelioma. (2015)
  • Author(s): Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Luk H, Baumann F, Zhang YA, Gazdar A, Kanodia S, Tiirikainen M, Flores E, Gaudino G, Becich MJ, Pass HI, Yang H, Carbone M.
  • Journal Title: Journal of thoracic oncology Volume: 10 Issue: 4 Pages: 565-576
  • DOI: 10.1097/jto.0000000000000471
  • Peer Reviewed
• [Presentation] Differences with BAP1- and PBRM1-mutations among malignant mesotheliomas and renal cell carcinomas (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