Analysis of somatic alteration of copy number variation in cancer as a new instability of cancer

• Project/Area Number: 26640121
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Medical genome science
• Research Institution: The University of Tokyo
• Principal Investigator: MURAKAMI Yoshinori 東京大学, 医科学研究所, 教授 (30182108)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: コピー数多型 / 乳がん / DNA コピー数多型 / 胆道がん / 不安定性 / がん遺伝子 / 癌細胞 / コピー数異常 / ゲノム不安定性 / 染色体不安定性 / 乳癌

Outline of Final Research Achievements

Somatic alterations of copy number variation (CNV), a new DNA polymorphism, were analyzed in 52 tumors, including breast, tongue and bladder cancer and cholangiocarcinoma, using CNV-specific arrays in order to elucidate their molecular feature, pathological significance and resulted genetic alterations. We demonstrated that somatic alterations of CNV in the fragments of less than 10kb occurred independently of those in the fragments of more than 1Mb and defined as CNV instability. CNV instability was observed in 10-20% of 4 cancers, especially those in advanced stages. Genetic alterations caused by somatic CNV alterations were also examined in breast cancers and a number of candidate genes were identified. Analysis of somatic CNV alteration would provide a novel approach to identify critical genes as well as a new pathway in the development and progression of human cancer.

Research Products

• [Int'l Joint Research] Johns Hopkins University/Texas University/University of Utah(米国)
• [Int'l Joint Research] Khon Kaen University(Thailand)
• [Journal Article] NECAB3 Promotes Activation of Hypoxia-inducible factor-1 during Normoxia and Enhances Tumourigenicity of Cancer Cells (2016)
  • Author(s): 1.Nakaoka HJ, Hara T, Yoshino S, Kanamori A, Matsui Y, Shimamura T, Sato H, Murakami Y, Seiki M, Sakamoto T
  • Journal Title: Sci Rep Volume: 6 Issue: 1 Pages: 22784-22784
  • DOI: 10.1038/srep22784
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CRTAM determines the CD4+ cytotoxic T lymphocyte lineage. (2016)
  • Author(s): Takeuchi, A., Badr Mel, S., Miyauchi, K., Ishihara, C., Onishi, R., Guo, Z., Sasaki. Y., Ike, H., Takumi, A., Tsuji, NM., Murakami, Y., Katakai, T., Kubo, M. and Saito, T.
  • Journal Title: J. Exp. Med. Volume: 213 Issue: 1 Pages: 123-138
  • DOI: 10.1084/jem.20150519
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Frequent copy gain of the MET gene in hypopharyngeal and larynxeal cancer in the Japanese population (2015)
  • Author(s): Akashi K, Ebihara Y, Omura G, Saito Y, Yoshida M, Ando M, Asakage T, Yamasoba T, Murakami Y
  • Journal Title: Journal of Cancer Therapy Volume: 6 Issue: 12 Pages: 1093-1102
  • DOI: 10.4236/jct.2015.612119
  • Peer Reviewed / Open Access
• [Journal Article] A measles virus selectively blind to signaling lymphocytic activation molecule shows anti-tumor activity against lung cancer cells. (2015)
  • Author(s): Fujiyuki T, Yoneda M, Amagai Y, Obayashi K, Ikeda F, Shoji K, Murakami Y, Sato H, Kai C.
  • Journal Title: Oncotarget, Volume: 6 Issue: 28 Pages: 24895-24903
  • DOI: 10.18632/oncotarget.4366
  • Peer Reviewed / Open Access
• [Journal Article] Dynamic Regulation of a Cell Adhesion Protein Complex Including CADM1 by Combinatorial Analysis of FRAP with Exponential Curve-fitting (2015)
  • Author(s): Sakurai-Yageta, M., Maruyama,T., Suzuki, T., Ichikawa, K., and Murakami, Y.
  • Journal Title: PLoS ONE Volume: 10 Issue: 3 Pages: 0116637-0116637
  • DOI: 10.1371/journal.pone.0116637
  • Peer Reviewed / Open Access
• [Journal Article] Promoter Methylation of the CADM1 and 4.1B Genes Occurs Independently of the EGFR or the KRAS2 Mutation in Non-Small Cell Lung Cancer. (2015)
  • Author(s): Hiroyuki Kogai, Shinji Kikuchi, Takashi Obana, Yumi Tsuboi, Tomoko Maruyama, Mika Sakurai-Yageta, Hisao Asamura, Yae Kanai, Yoshinori Murakami.
  • Journal Title: Journal of Cancer Therapy. Volume: 6 Issue: 03 Pages: 273-285
  • DOI: 10.4236/jct.2015.63030
  • Peer Reviewed / Open Access
• [Journal Article] Immunohistochemical analysis of the expression of E-cadherin and ZEB1 in non-small cell lung cancer. (2014)
  • Author(s): Matsubara D, Kishaba Y, Yoshimoto T, Sakuma Y, Sakatani T, Tamura T, Endo S, Sugiyama Y, Murakami Y, Niki T
  • Journal Title: Pathology International Volume: 64 Issue: 11 Pages: 560-568
  • DOI: 10.1111/pin.12214
  • Peer Reviewed / Open Access
• [Journal Article] High incidence of null-type mutations of the TP53 gene in Japanese patients with head and neck squamous cell carcinoma. (2014)
  • Author(s): Ebihara Y, Iwai M, Akashi K, Ito T, Omura G, Saito Y, Yoshida M, Ando M, Asakage T, Yamasoba T, Murakami Y.
  • Journal Title: Journal of Cancer Therapy Volume: 5 Pages: 664-671
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Detection of lung tumors in mice using a 1-Tesla compact magnetic resonance imaging system. (2014)
  • Author(s): Wang F, Akashi K, Murakami Y, Inoue Y, Furuta T, Yamada H, Ohtomo K, Kiryu S.
  • Journal Title: PLoS One, Volume: 9 Issue: 4 Pages: e94945-e94945
  • DOI: 10.1371/journal.pone.0094945
  • Peer Reviewed / Open Access
• [Journal Article] Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition. (2014)
  • Author(s): Ibrahim R, Matsubara D, Osman W, Morikawa T, Goto A, Morita S, Ishikawa S, Aburatani H, Takai D, Nakajima J, Fukayama M, Niki T, Murakami Y
  • Journal Title: Hum Pathol. Volume: 45 Issue: 7 Pages: 1397-405
  • DOI: 10.1016/j.humpath.2014.02.013
  • Peer Reviewed / Open Access
• [Journal Article] CRTAM controls residency of gut CD4+CD8+T cells in the steady state and maintenance of gut CD4 TH17 during parasitic infection. (2014)
  • Author(s): Cortez VS, Cervantes-Barragan L, Song C, Gilfillan S, McDonald KG, Edelson BT, Murakami Y, Newberry RD, Sibley LD, Colonna M.
  • Journal Title: J Exp. Med. Volume: 211 Issue: 4 Pages: 623-633
  • DOI: 10.1084/jem.20130904
  • Peer Reviewed / Open Access
• [Journal Article] Trans-homophilic interaction of CADM1 activates PI3K by forming a complex with MAGuK-family proteins MPP3 and Dlg. (2014)
  • Author(s): Murakami, S., Sakurai-Yageta, M. (equal contribution), Maruyama, T., Murakami, Y.
  • Journal Title: PloS One Volume: 9(2) Issue: 2 Pages: e82894-e82894
  • DOI: 10.1371/journal.pone.0082894
  • Peer Reviewed / Open Access
• [Presentation] Mathematical analysis of the dynamics of CADM1 and its role in the MET-driven resistance against EGFR-TKI in lung adenocarcinoma. (2016)
  • Author(s): Ito T, Sakurai-Yageta M, Tsuchiya T, Kawasaki S, Ohba M, Ichikawa K, Suzuki T, Murakami Y.
  • Organizer: The First JSPS Core-to-Core Seminar: Establishing Research Network of Mathematical Oncology.
  • Place of Presentation: 大和高原ボスコヴィラ(奈良県奈良市）
  • Year and Date: 2016-03-08
  • Int'l Joint Research
• [Presentation] Dual roles of a Cell Adhesion Molecule CADM1 in Oncogenesis. (2016)
  • Author(s): Ito T, Tsuchiya T, Kumagai Y, Tsuboi Y, Sakurai-Yageta M, Oba M and Murakami Y.
  • Organizer: The 10th AACR-JCA Joint Symposium of Cancer Research
  • Place of Presentation: Maui, Hawai, USA
  • Year and Date: 2016-02-14
  • Int'l Joint Research
• [Presentation] Roles of a cell adhesion molecule CADM1 in apoptosis induction, invasion and metastasis. (2015)
  • Author(s): Murakami Y, Ito T, Kogai H, Sakurai-Yageta M, Kumagai Y, Matsubara D.
  • Organizer: The 74th Annual Meeting of Japanese Cancer Association. Symposium
  • Place of Presentation: 名古屋国際会議場（愛知県名古屋市）
  • Year and Date: 2015-10-08
  • Invited
• [Presentation] Roles of a cell adhesion molecule CADM1 in apoptosis induction, invasion and metastasis. (2015)
  • Author(s): Murakami Y, Matsuda K, Kubo M.
  • Organizer: 東京大学ゲノム医科学研究機構キックオフ・シンポジウム
  • Place of Presentation: 伊藤国際学術研究センター（東京都文京区）
  • Year and Date: 2015-08-29
  • Invited
• [Presentation] Analysis of the role of CADM1 in suppression of lung cancer using Cadm1-deficient mice. (2015)
  • Author(s): Ito T, Nagata M, Kawai T, Maruyama T, Sakurai-Yageta M, Ito A, Goto A, Matsubara D, Murakami Y.
  • Organizer: AACR Annual Meeting
  • Place of Presentation: Philadelphia, PA, USA
  • Year and Date: 2015-04-16
  • Int'l Joint Research
• [Presentation] Genomic and transcriptional alterations of cholangiocarcinoma. (2015)
  • Author(s): Ito T, Sakurai-Yageta M, Goto A, Murakami Y.
  • Organizer: The 1st International Symposium for Biomarkers of Cholangiocarcinoma
  • Place of Presentation: 東京都新宿区
  • Year and Date: 2015-01-24
  • Invited
• [Presentation] Involvement of CADM1 in apoptosis induction of detached epithelial cells as a new type of dependence receptor. (2014)
  • Author(s): Kogai H, Sakurai-Yageta M, Delloye-Bourgeois C, Tauszig-Delamasure S, Mehlen P, Murakami Y.
  • Organizer: 4th France-Japan Cancer Workshop
  • Place of Presentation: 京都府京都市
  • Year and Date: 2014-11-18 – 2014-11-21
  • Invited
• [Presentation] Involvement of a cell adhesion molecule CADM1 in oncogenesis. (2014)
  • Author(s): Murakami Y.
  • Organizer: The 2nd International Alliance Research Internship Program Symposium of the University of Lyon.
  • Place of Presentation: フランス リヨン市
  • Year and Date: 2014-11-03 – 2014-11-04
  • Invited
• [Presentation] Involvement of CADM1 in apoptosis induction of detached epithelial cells as a new type of dependence receptor. (2014)
  • Author(s): Kogai H, Sakurai-Yageta M, Tauszig-Delamasure S, Mehlen P, Murakami Y.
  • Organizer: The 20th International Charles Heidelberger Symposium on Cancer Research、
  • Place of Presentation: チリ アリカ市
  • Year and Date: 2014-10-08 – 2014-10-11
  • Invited
• [Presentation] Roles of a cell adhesion molecule CADM1 in epithelial integrity and malignant phenotype of cancer cells. (2014)
  • Author(s): Murakami Y.
  • Organizer: The 73rd Annual Meeting of Japanese Cancer Association
  • Place of Presentation: 神奈川県 横浜市
  • Year and Date: 2014-09-25 – 2014-09-27
  • Invited
• [Presentation] Context dependent features of a cell adhesion molecule CADM1 in human oncogenesis. (2014)
  • Author(s): Ito T, Kogai H,Murakami S, Sakurai-Yageta M, Matsubara D, Murakami Y.
  • Organizer: The 21st East Asia Joint Conference
  • Place of Presentation: 韓国 京城市
  • Year and Date: 2014-07-15 – 2014-07-18
  • Invited
• [Remarks] 東京大学医科学研究所 人癌病因遺伝子分野
  • URL: http://www.ims.u-tokyo.ac.jp/hitogan/index.html
• [Remarks] 東京大学医科学研究所人癌病因遺伝子分野
  • URL: http://www.ims.u-tokyo.ac.jp/hitogan/index.html