Development of cancer diagnostics based on genomic information

2009 Fiscal Year Final Research Report

• Project/Area Number: 17015008
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: ABURATANI Hiroyuki The University of Tokyo, 先端科学技術研究センター, 教授 (10202657)
• Project Period (FY): 2005 – 2009
• Keywords: ゲノム / がん / 遺伝子 / マイクロアレイ / エピゲノム / DNAメチル化 / 染色体欠失

Research Abstract

Integrated analysis of gene expression, genomic copy number and DNA methylation profiles has enabled stratification of cancer patients and will be crucial in applying personalized treatment.

Research Products

• [Journal Article] Identification of genes preferentially methylated in hepatitis C virus-related hepatocellular carcinoma. (2010)
  • Author(s): Deng YB, Nagae G, Midorikawa Y, Yagi K, Tsutsumi S, Yamamoto S, Hasegawa K, Kokudo N, Aburatani H, Kaneda A.
  • Journal Title: Cancer Sci. (Epub ahead of print)
• [Journal Article] Identification of chromosomal aberrations of metastatic potential in colorectal carcinoma. (2010)
  • Author(s): Yamamoto S, Midorikawa Y, Morikawa T, Nishimura Y, Sakamoto H, Ishikawa S, Akagi K, Aburatani H.
  • Journal Title: Genes Chromosomes Cancer. 49(5) Pages: 487-96
• [Journal Article] Genome-wide single nucleotide polymorphism arrays in endometrial carcinomas associate extensive chromosomal instability with poor prognosis and unveil frequent chromosomal imbalances involved in PI3-kinase pathway. (2010)
  • Author(s): Murayama-Hosokawa S, Oda K, Nakagawa S, Ishikawa S, Yamamoto S, Shoji K, Ikeda Y, Uehara Y, Fukayama M, McCormick F, Yano T, Taketani Y, Aburatani H.
  • Journal Title: Oncogene 29(13) Pages: 1897-908
• [Journal Article] Three DNA Methylation Epigenotypes in Human Colorectal Cancer. (2010)
  • Author(s): Yagi K, Akagi K, Hayashi H, Nagae G, Tsuji S, Isagawa T, Midorikawa Y, Nishimura Y, Sakamoto H, Seto Y, Aburatani H, Kaneda A.
  • Journal Title: Clin Cancer Res. 16(1) Pages: 21-33
• [Journal Article] The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. (2009)
  • Author(s): Shoji K, Oda K, Nakagawa S, Hosokawa S, Nagae G, Uehara Y, Sone K, Miyamoto Y, Hiraike H, Hiraike-Wada O, Nei T, Kawana K, Kuramoto H, Aburatani H, Yano T, Taketani Y.
  • Journal Title: Br J Cancer. 101(1) Pages: 145-8
• [Journal Article] Glypican-3 expression in clear cell adenocarcinoma of the ovary., Chauhan SC, Vannatta K, Ebeling MC, Vinayek N, Watanabe A, Pandey KK, Bell MC, Koch MD, Aburatani H, Lio Y, Jaggi M. Expression and functions of transmembrane mucin MUC13 in ovarian cancer. (2009)
  • Author(s): Maeda D, Ota S, Takazawa Y, Aburatani H, Nakagawa S, Yano T, Taketani Y, Kodama T, Fukayama M.
  • Journal Title: Mod Pathol., Cancer Res. 22(6),69(3) Pages: 824-32,765-74
• [Journal Article] Allelic imbalances and homozygous deletion on 8p23. 2 for stepwise progression of hepatocarcinogenesis. (2009)
  • Author(s): Midorikawa Y, Yamamoto S, Tsuji S, Kamimura N, Ishikawa S, Igarashi H, Makuuchi M, Kokudo N, Sugimura H, *Aburatani H.
  • Journal Title: Hepatology. 49(2) Pages: 513-22
• [Journal Article] Anti-glypican 3 antibodies cause ADCC against human hepatocellular carcinoma cells. (2009)
  • Author(s): Nakano K, Orita T, Nezu J, Yoshino T, Ohizumi I, Sugimoto M, Furugaki K, Kinoshita Y, Ishiguro T, Hamakubo T, Kodama T, Aburatani H, Yamada-Okabe H, Tsuchiya M.
  • Journal Title: Biochem Biophys Res Commun. 378(2) Pages: 279-84
• [Journal Article] Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer. (2008)
  • Author(s): Ishiguro T, Sugimoto M, Kinoshita Y, Miyazaki Y, Nakano K, Tsunoda H, Sugo I, Ohizumi I, Aburatani H, Hamakubo T, Kodama T, Tsuchiya M, Yamada-Okabe H.
  • Journal Title: ancer Res. 68(23) Pages: 9832-8
• [Journal Article] The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. (2008)
  • Author(s): Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, Maru Y.
  • Journal Title: Nat Cell Biol. 10(11) Pages: 1349-55
• [Journal Article] Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is regulated transcriptionally by beta-catenin/TCF. (2008)
  • Author(s): Torisu Y, Watanabe A, Nonaka A, Midorikawa Y, Makuuchi M, Shimamura T, Sugimura H, Niida A, Akiyama T, Iwanari H, Kodama T, Zeniya M, *Aburatani H.
  • Journal Title: Cancer Sci. 99(6) Pages: 1139-46
• [Journal Article] Constitutive activation of c-Met is correlated with c-Met overexpression and dependent on cell-matrix adhesion in lung adenocarcinoma cell lines. (2008)
  • Author(s): Nakamura Y, Matsubara D, Goto A, Ota S, Sachiko O, Ishikawa S, Aburatani H, Miyazawa K, Fukayama M, Niki T.
  • Journal Title: Cancer Sci. 99(1) Pages: 14-22
• [Journal Article] Identification of toll-like receptor 3 as a potential therapeutic target in clear cell renal cell carcinoma. (2007)
  • Author(s): Morikawa T, Sugiyama A, Kume H, Ota S, Kashima T, Tomita K, Kitamura T, Kodama T, Fukayama M, Aburatani H.
  • Journal Title: Clin Cancer Res. 13(19) Pages: 5703-9
• [Journal Article] High-density oligonucleotide array with sub-kilobase resolution reveals breakpoint information of submicroscopic deletions in nevoid basal cell carcinoma syndrome. (2007)
  • Author(s): Fujii K, Ishikawa S, Uchikawa H, Komura D, Shapero MH, Shen F, Hung J, Arai H, Tanaka Y, Sasaki K, Kohno Y, Yamada M, Jones KW, Aburatani H, Miyashita T.
  • Journal Title: Hum Genet. 122(5) Pages: 459-66
• [Journal Article] Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. (2007)
  • Author(s): Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara SI, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H.
  • Journal Title: Nature. 448(7153) Pages: 561-6
• [Journal Article] Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis. (2007)
  • Author(s): Takayama K, Kaneshiro K, Tsutsumi S, Horie-Inoue K, Ikeda K, Urano T, Ijichi N, Ouchi Y, Shirahige K, Aburatani H, Inoue S.
  • Journal Title: Oncogene. 26(30) Pages: 4453-63
• [Journal Article] Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. (2006)
  • Author(s): Hiratsuka S, Watanabe A, Aburatani H, Maru Y.
  • Journal Title: Nat Cell Biol. 8(12) Pages: 1369-75
• [Journal Article] Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein-producing gastric carcinoma. (2006)
  • Author(s): Hishinuma M, Ohashi KI, Yamauchi N, Kashima T, Uozaki H, Ota S, Kodama T, Aburatani H, Fukayama M.
  • Journal Title: Histopathology. 49(5) Pages: 479-86
• [Journal Article] Oncofetal protein glypican-3 in testicular germ-cell tumor. (2006)
  • Author(s): Ota S, Hishinuma M, Yamauchi N, Goto A, Morikawa T, Fujimura T, Kitamura T, Kodama T, Aburatani H, Fukayama M.
  • Journal Title: Virchows Arch. 449(3) Pages: 308-14
• [Journal Article] Copy number variation: New insights in genome diversity. (2006)
  • Author(s): Freeman JL, Perry GH, Feuk L, Redon R, McCarroll SA, Altshuler DM, Aburatani H, Jones KW, Tyler-Smith C, Hurles ME, Carter NP, Scherer SW, Lee C.
  • Journal Title: Genome Res. 16(8) Pages: 949-61
• [Journal Article] Noise Reduction from genotyping microarrays using probe level information. (2006)
  • Author(s): Komura D, Nishimura K, Ishikawa S, Panda B, Huang J, Nakamura H, Ihara S, Hirose M, Jones KW, Aburatani H.
  • Journal Title: In Silico Biol. 6(1-2) Pages: 79-92
• [Journal Article] Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays. (2006)
  • Author(s): Midorikawa Y, Yamamoto S, Ishikawa S, Kamimura N, Igarashi H, Sugimura H, Makuuchi M, Aburatani H.
  • Journal Title: Oncogene. 25(40) Pages: 5581-90
• [Journal Article] Identification of ROBO1 as a Novel Hepatocellular Carcinoma Antigen and a Potential Therapeutic and Diagnostic Target. (2006)
  • Author(s): Ito H, Funahashi S, Yamauchi N, Shibahara J, Midorikawa Y, Kawai S, Kinoshita Y, Watanabe A, Hippo Y, Ohtomo T, Iwanari H, Nakajima A, Makuuchi M, Fukayama M, Hirata Y, Hamakubo T, Kodama T, Tsuchiya M, Aburatani H.
  • Journal Title: Clin Cancer Res. 12(11) Pages: 3257-64
• [Journal Article] A new melanoma antigen Fatty Acid-binding protein 7, involved in proliferation and invasion, is a potential target for immunotherapy and molecular target therapy. (2006)
  • Author(s): Goto Y, Matsuzaki Y, Kurihara S, Shimizu A, Okada T, Yamamoto K, Murata H, Takata M, Aburatani H, Hoon DS, Saida T, Kawakami Y.
  • Journal Title: Cancer Res. 66(8) Pages: 4443-9
• [Journal Article] Hepatocellular carcinoma in Txnip-deficient mice. (2006)
  • Author(s): Sheth SS, Bodnar JS, Ghazalpour A, Thipphavong CK, Tsutsumi S, Tward AD, Demant P, Kodama T, Aburatani H, Lusis AJ.
  • Journal Title: Oncogene. 25(25) Pages: 3528-36
• [Journal Article] CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays. (2006)
  • Author(s): Huang J, Wei W, Chen J, Zhang J, Liu G, Di X, Mei R, Ishikawa S, Aburatani H, Jones KW, Shapero MH.
  • Journal Title: BMC Bioinformatics. 7(1) Pages: 83
• [Journal Article] Chromosomal Numerical Abnormality Profiles of Gastrointestinal Stromal Tumors. (2006)
  • Author(s): Yamashita K, Igarashi H, Kitayama Y, Ozawa T, Kiyose S, Konno H, Kazui T, Ishikawa S, Aburatani H, Tanioka F, Suzuki M, Sugimura H.
  • Journal Title: Jpn J Clin Oncol. 36(2) Pages: 85-92
• [Journal Article] Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer. (2006)
  • Author(s): Tanaka T, Jiang S, Hotta H, Takano K, Iwanari H, Sumi K, Daigo K, Ohashi R, Sugai M, Ikegame C, Umezu H, Hirayama Y, Midorikawa Y, Hippo Y, Watanabe A, Uchiyama Y, Hasegawa G, Reid P, Aburatani H, Hamakubo T, Sakai J, Naito M, Kodama T.
  • Journal Title: J Pathol. 208(5) Pages: 662-672
• [Journal Article] Elevated expression and potential roles of human Sp5, a member of Sp transcription factor family, in human cancers. (2006)
  • Author(s): Chen Y, Guo Y, Ge X, Itoh H, Watanabe A, Fujiwara T, Kodama T, Aburatani H.
  • Journal Title: Biochem Biophys Res Commun. 340(3) Pages: 758-66
• [Journal Article] Topological and functional discovery in a gene coexpression meta-network of gastric cancer. (2006)
  • Author(s): Aggarwal A, Li Guo D, Hoshida Y, Tsan Yuen S, Chu KM, So S, Boussioutas A, Chen X, Bowtell D, Aburatani H, Leung SY, Tan P.
  • Journal Title: Cancer Res. 66(1) Pages: 232-41
• [Journal Article] Differential expression of S100A2 and S100A4 in lung adenocarcinomas: Clinicopathological significance, relationship to p53 and identification of their target genes. (2005)
  • Author(s): Matsubara D, Niki T, Ishikawa S, Goto A, Ohara E, Yokomizo T, Heizmann CW, Aburatani H, Moriyama S, Moriyama H, Nishimura Y, Funata N, Fukayama M.
  • Journal Title: Cancer Sci. 96(12) Pages: 844-57
• [Journal Article] Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization. (2005)
  • Author(s): Inamura K, Fujiwara T, Hoshida Y, Isagawa T, Jones MH, Virtanen C, Shimane M, Satoh Y, Okumura S, Nakagawa K, Tsuchiya E, Ishikawa S, Aburatani H, Nomura H, Ishikawa Y.
  • Journal Title: Oncogene. 24(47) Pages: 7105-13
• [Journal Article] Allelic dosage analysis with genotyping microarrays. (2005)
  • Author(s): Ishikawa S, Komura D, Tsuji S, Nishimura K, Yamamoto S, Panda B, Huang J, Fukayama M, Jones KW, Aburatani H.
  • Journal Title: Biochem Biophys Res Commun. 333(4) Pages: 1309-1314
• [Journal Article] Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells. (2005)
  • Author(s): Yokoyama K, Higashi H, Ishikawa S, Fujii Y, Kondo S, Kato H, Azuma T, Wada A, Hirayama T, Aburatani H, Hatakeyama M.
  • Journal Title: Proc Natl Acad Sci U S A. 102(27) Pages: 9661-6
• [Journal Article] Interpreting expression profiles of cancers by genome-wide survey of breadth-of-expression in normal tissues. (2005)
  • Author(s): Ge X, Yamamoto S, Tsutsumi S, Midorikawa Y, Ihara S, Wang SM, Aburatani H.
  • Journal Title: Genomics 86(2) Pages: 127-141
• [Journal Article] The Glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. (2005)
  • Author(s): Yamauchi N, Watanabe A, Hishinuma M, Ohashi KI, Midorikawa Y, Morishita Y, Niki T, Shibahara J, Mori M, Makuuchi M, Hippo Y, Kodama T, Iwanari H, Aburatani H, Fukayama M.
  • Journal Title: Modern Pathology 18(12) Pages: 1591-8
• [Journal Article] Overexpression of MUC13 is associated with intestinal-type gastric cancer. (2005)
  • Author(s): Shimamura T, Ito H, Shibahara J, Watanabe A, Hippo Y, Taniguchi H, Chen Y, Kashima T, Ohtomo T, Tanioka F, Iwanari H, Kodama T, Kazui T, Sugimura H, Fukayama M, Aburatani H.
  • Journal Title: Cancer Sci. 96(5) Pages: 265-73
• [Journal Article] Paired-like homeoprotein ESXR1 acts as a sequence-specific transcriptional repressor of the human K-ras gene. (2005)
  • Author(s): Yanagihara M, Ishikawa S, Naito M, Nakajima J, Aburatani H, Hatakeyama M.
  • Journal Title: Oncogene 24(38) Pages: 5878-87
• [Presentation] Epigenetic dynamics. (2009)
  • Organizer: 2009 International Conference on Genomics -Human and Beyond
  • Place of Presentation: henzhen, China
  • Year and Date: 20091103-20091105
• [Presentation] Integrated analysis of genomic, epigenomic alterations in liver cancer. (2009)
  • Organizer: Personal genomes
  • Place of Presentation: Cold Spring Harbor
  • Year and Date: 20090914-20090917
• [Presentation] Cancer genome, epigenome. (2009)
  • Organizer: HGM2007 Workshop : Cancer Genomics
  • Place of Presentation: Montreal
  • Year and Date: 20090521-20090524
• [Presentation] Epigenomic profiling of cancer. (2009)
  • Organizer: Epigenetics in Development and Diseases Conference : 4th Asian Epigenomics Meeting
  • Place of Presentation: Singapore
  • Year and Date: 2009-08-25
• [Presentation] Regulatory genomics : allelic variaion in transcriptional variation. (2008)
  • Organizer: JST-ETH Zurich workshop on Medical Research
  • Place of Presentation: Zurich
  • Year and Date: 20080915-20080916
• [Presentation] Epigenomic profiling : Global DNA methylation profiles in differentiation from ES cells. (2008)
  • Organizer: 7th Human Genome Organization (HUGO)-Pacific meeting
  • Place of Presentation: Cebu
  • Year and Date: 2008-04-02
• [Presentation] Genomic, epigenomic profiling in cancer. (2007)
  • Organizer: AACR Centennial Conference Concurrent session : Systems Medicine
  • Place of Presentation: Singapore
  • Year and Date: 20071104-20071108
• [Presentation] エピゲノム解析 (2007)
  • Organizer: 第66回日本癌学会総会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-05
• [Presentation] Copy number variation in human genome. (2007)
  • Organizer: AACR Annual Meeting 2007 Method Workshop‘Interpreting Chromosomal Copy Number Aberrations'
  • Place of Presentation: Los Angeles
  • Year and Date: 2007-04-14
• [Presentation] アレイを用いた網羅的エピゲノム解析 (2006)
  • Organizer: 第65回日本癌学会学術総会シンポジウム「ゲノミクス・プロテオミクスによる大規模解析とその臨床応用」
  • Place of Presentation: 横浜
  • Year and Date: 2006-09-30
• [Presentation] Glypican-3 as a novel diagnostic, therapeutic target for hepatocellular carcinoma. (2006)
  • Organizer: Gordon Research Conference (Proteoglycans)
  • Place of Presentation: 米国
  • Year and Date: 2006-07-14
• [Remarks]
  • URL: http://www.genome.rcast.u-tokyo.ac.jp/
• [Patent(Industrial Property Rights)] 抗Desmoglein3抗体を用いる癌の診断および治療 (2007)
  • Inventor(s): 川合重人、中野清孝、伊藤浩孝、油谷浩幸、石川俊平
  • Industrial Property Rights Holder: 東京大学、未来創薬研究所
  • Industrial Property Number: 特許権特願2007-19108
  • Filing Date: 2007-01-30
• [Patent(Industrial Property Rights)] 遺伝子コピーの解析方法及び装置 (2005)
  • Inventor(s): 油谷浩幸、石川俊平、西村邦裕、河村大輔
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Industrial Property Number: 特許権PCT/JP2005/16451
  • Filing Date: 2005-09-07