Study on the mechanism underlying the centrosome amplification induced by DNA repair abnormality in cancer

• Project/Area Number: 25460476
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Shinmura Kazuya 浜松医科大学, 医学部, 准教授 (40321880)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Centrosome amplification / DNA repair / SASS6 / SGOL1 / NEIL / MUTYH / STK15 / 中心体 / WDR62 / DNAグリコシラーゼ / 中心体過剰複製 / ラギング染色体 / 染色体不安定性 / 予後不良因子 / TDG / DNA修復酵素遺伝子 / DNA付加体 / MUTYH関連ポリポーシス / 遺伝子増幅

Outline of Final Research Achievements

The followings were revealed in this study: (1) Abnormality of a part of DNA repair gene is associated with centrosome amplification. (2) SASS6 overexpression is associated with centrosome amplification, mitotic chromosomal abnormalities, chromosome instability, and a poor prognosis in patients with colorectal cancer. (3) Overexpression of a SGOL1 splicing variant type B (SGOL1-B) is associated with centrosome amplification, abnormal mitosis, and resistance to taxane in non-small cell lung cancer. (4) Amplification of STK15（AURAK）gene which is involved in the centrosome regulation is a predictor of a poor prognosis in patients with gastric cancer. (5) Abnormal expressions of DNA glycosylase genes NEIL1, NEIL2, and NEIL3 are associated with somatic mutation loads in human cancer.

Research Products

• [Journal Article] Functional Evaluation of Nine Missense-Type Variants of the Human DNA Glycosylase Enzyme MUTYH in the Japanese Population. (2016)
  • Author(s): Shinmura K, Kato H, Goto M, Yamada H, Tao H, Nakamura S, Sugimura H.
  • Journal Title: Hum Mutat. Volume: 37 Issue: 4 Pages: 350-353
  • DOI: 10.1002/humu.22949
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are Associated with Somatic Mutation Loads in Human Cancer. (2016)
  • Author(s): Shinmura K, Kato H, Kawanishi Y, Igarashi H, Goto M, Tao H, Inoue Y, Nakamura S, Misawa K, Mineta H, Sugimura H.
  • Journal Title: Oxidative Medicine and Cellular Longevity Volume: 2016 Issue: 1 Pages: 1546392-1546392
  • DOI: 10.1155/2016/1546392
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] SASS6 overexpression is associated with mitotic chromosomal abnormalities and a poor prognosis in patients with colorectal cancer (2015)
  • Author(s): Shinmura K, Kato H, Kawanishi Y, Nagura K, Kamo T, Okubo Y, Inoue Y, Kurabe N, Du C, Iwaizumi M, Kurachi K, Nakamura T, Sugimura H
  • Journal Title: Oncology Reports Volume: 印刷中
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Human DNA glycosylase enzyme TDG repairs thymine mispaired with exocyclic etheno-DNA adducts (2014)
  • Author(s): Goto M, Shinmura K, Matsushima Y, Ishino K, Yamada H, Totsuka Y, Matsuda T, Nakagama H, Sugimura H
  • Journal Title: Free Radical Biology and Medicine Volume: 76 Pages: 136-146
  • DOI: 10.1016/j.freeradbiomed.2014.07.044
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In silico evaluation of nonsynonymous single nucleotide polymorphisms in the TDG gene, which is involved in base excision repair (2014)
  • Author(s): Shinmura K, Kato H, Goto M, Du C, Inoue Y, Nakamura S, Sugimura H
  • Journal Title: Annals of Clinical Pathology Volume: 2 Pages: 1014-1014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PLK4 overexpression and its effect on centrosome regulation and chromosome stability in human gastric cancer (2014)
  • Author(s): Shinmura K, Kurabe N, Goto M, Yamada H, Natsume H, Konno H, Sugimura H
  • Journal Title: Molecular Biology Reports Volume: 41 Issue: 10 Pages: 6635-6644
  • DOI: 10.1007/s11033-014-3546-2
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] TNK2 gene amplification is a novel predictor of a poor prognosis in patients with gastric cancer (2014)
  • Author(s): Shinmura K, Sugimura H et al.
  • Journal Title: J Surg Oncol Volume: 109(3) Issue: 3 Pages: 189-97
  • DOI: 10.1002/jso.23482
  • Peer Reviewed / Open Access
• [Journal Article] Impaired 8-hydroxyguanine repair activity of MUTYH variant p. Arg109Trp found in a Japanese patient with early-onset colorectal cancer (2014)
  • Author(s): Shinmura, K., Goto, M., Tao, H., Kato, H., Suzuki, R., Nakamura, S., Matsuda, T., Yin, G., Morita, M., Kono, S., Sugimura, H.
  • Journal Title: Oxidative Medicine and Cellular Longevity Volume: 2014 Pages: 617351-617351
  • DOI: 10.1155/2014/617351
  • Peer Reviewed / Open Access
• [Journal Article] SGOL1 variant B induces abnormal mitosis and resistance to taxane in non-small cell lung cancers (2013)
  • Author(s): Matsuura S, Kahyo T, Shinmura K, Iwaizumi M, Yamada H, Funai K, Kobayashi J, Tanahashi M, Niwa H, Ogawa H, Takahashi T, Inui N, Suda T, Chida K, Watanabe Y, *Sugimura H.
  • Journal Title: Sci Rep Volume: 3 Issue: 1 Pages: 3012-3012
  • DOI: 10.1038/srep03012
  • Peer Reviewed / Open Access
• [Presentation] SASS6高発現は大腸癌のM期染色体異常と患者予後不良と関連性を示す (2015)
  • Author(s): 新村和也, 加藤寿美, 川西祐一, 加茂隆春, 井上裕介, 倉部誠也, 杜春平, 倉地清隆, 中村利夫, 椙村春彦.
  • Organizer: 第104回日本病理学会総会
  • Place of Presentation: 名古屋市
  • Year and Date: 2015-04-30
• [Presentation] SGOL1 variant B induces abnormal mitosis and resistance to taxane in non-small cell lung cancers (2014)
  • Author(s): Matsuura S, Kahyo T, Shinmura K, Iwaizumi M, Yamada H, Funai K, Niwa H, Takahashi T, Suda T, Watanabe Y, Sugimura H
  • Organizer: 73th Annual Meeting of the Japanese Cancer Association
  • Place of Presentation: パシフィコ横浜 神奈川県横浜市
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 日本人若年発症大腸がん患者で見つけられた低8-hydroxyguanine修復・突然変異制御活性を示すMUTYH variant (2014)
  • Author(s): 新村和也, 後藤正憲, 後藤正憲, 陶弘, 加藤寿美, 中村悟己, 松田知成, 椙村春彦
  • Organizer: 第67回日本酸化ストレス学会学術集会
  • Place of Presentation: 同志社大学 京都府京都市
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] 日本人若年発症大腸がん患者で見つけられた低8-hydroxyguanine修復・突然変異制御活性を示すMUTYH variant (2014)
  • Author(s): 新村和也、後藤正憲、陶弘、加藤寿美、中村悟己、松田知成、椙村春彦
  • Organizer: 第103回日本病理学会総会
  • Place of Presentation: 広島