Germline mutations causing familial lung cancer

• Project/Area Number: 25462180
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Nagasaki University
• Principal Investigator: MIYAZAKI Takuro 長崎大学, 病院(医学系), 助教 (00584749)
• Co-Investigator(Kenkyū-buntansha): NAGAYASU Takeshi 長崎大学, 医歯薬学総合研究科(医学系), 教授 (80284686) ; TSUCHIYA Tomoshi 長崎大学, 医歯薬学総合研究科(医学系), 准教授 (30437884) ; MATSUMOTO Keitaro 長崎大学, 医歯薬学総合研究科(医学系), 講師 (80404268) ; KUBO Toru 長崎大学, 熱帯医学研究所, 客員研究員 (50444873)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 家族性肺癌 / exome解析

Outline of Final Research Achievements

To identify the gene(s) that cause lung cancer in this pedigree, we extracted DNA from the peripheral blood of three individuals and from the blood of one cancer-free control family member and performed whole-exome sequencing. We identified 41 alterations in 40 genes in all affected family members but not in the unaffected member. These were considered candidate mutations for familial lung cancer. Next, to identify somatic mutations and/orinherited alterations in these 40 genes among sporadic lung cancers, we performed exon target enrichment sequencing using 192 samples from sporadic lung cancer patients. We detected somatic ‘candidate’ mutations in multiple sporadic lung cancer samples; MAST1, CENPE, CACNB2 and LCT were the most promising candidate genes. In addition, the MAST1 gene was located in a putative cancer-linked locus in the pedigree. Our data suggest that several genes act as oncogenic drivers in this family, and that MAST1 is most likely to cause lung cancer.

Research Products

• [Journal Article] Germline mutations causing familial lung cancer. (2015)
  • Author(s): Tomoshige K, Matsumoto K, Tsuchiya T, Oikawa M, Miyazaki T, Yamasaki N, Mishima H, Kinoshita A, Kubo T, Fukushima K, Yoshiura K, Nagayasu T
  • Journal Title: J Hum Genet Volume: 60 Pages: 597-603
  • NAID: 40020621414
  • Peer Reviewed
• [Presentation] 次世代シーケンサーを用いたエキソーム解析による家族性肺癌責任遺伝子の同定
  • Author(s): 朝重耕一、宮崎拓郎、松本桂太郎、土谷智史、山崎直哉、永安武
  • Organizer: 第113回 日本外科学会
  • Place of Presentation: 福岡国際会議場(福岡市)