発現情報に基づくがん個性診断法の開発

2009 年度 研究成果報告書

• 研究課題/領域番号: 17015008
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 東京大学
• 研究代表者: 油谷 浩幸 東京大学, 先端科学技術研究センター, 教授 (10202657)
• 研究期間 (年度): 2005 – 2009
• キーワード: 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

研究概要

遺伝子発現、ゲノムコピー数、DNAメチル化情報を統合的に解析することによりがんを層別化することが可能であり、遺伝子変異解析もあわせて個別化医療を実践するために必要な診断の上でも重要である。

研究成果

• [雑誌論文] Identification of genes preferentially methylated in hepatitis C virus-related hepatocellular carcinoma. (2010)
  • 著者名/発表者名: Deng YB, Nagae G, Midorikawa Y, Yagi K, Tsutsumi S, Yamamoto S, Hasegawa K, Kokudo N, Aburatani H, Kaneda A.
  • 雑誌名: Cancer Sci. (Epub ahead of print)
• [雑誌論文] Identification of chromosomal aberrations of metastatic potential in colorectal carcinoma. (2010)
  • 著者名/発表者名: Yamamoto S, Midorikawa Y, Morikawa T, Nishimura Y, Sakamoto H, Ishikawa S, Akagi K, Aburatani H.
  • 雑誌名: Genes Chromosomes Cancer. 49(5) ページ: 487-96
• [雑誌論文] 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)
  • 著者名/発表者名: 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.
  • 雑誌名: Oncogene 29(13) ページ: 1897-908
• [雑誌論文] Three DNA Methylation Epigenotypes in Human Colorectal Cancer. (2010)
  • 著者名/発表者名: Yagi K, Akagi K, Hayashi H, Nagae G, Tsuji S, Isagawa T, Midorikawa Y, Nishimura Y, Sakamoto H, Seto Y, Aburatani H, Kaneda A.
  • 雑誌名: Clin Cancer Res. 16(1) ページ: 21-33
• [雑誌論文] The oncogenic mutation in the pleckstrin homology domain of AKT1 in endometrial carcinomas. (2009)
  • 著者名/発表者名: 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.
  • 雑誌名: Br J Cancer. 101(1) ページ: 145-8
• [雑誌論文] 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)
  • 著者名/発表者名: Maeda D, Ota S, Takazawa Y, Aburatani H, Nakagawa S, Yano T, Taketani Y, Kodama T, Fukayama M.
  • 雑誌名: Mod Pathol., Cancer Res. 22(6),69(3) ページ: 824-32,765-74
• [雑誌論文] Allelic imbalances and homozygous deletion on 8p23. 2 for stepwise progression of hepatocarcinogenesis. (2009)
  • 著者名/発表者名: Midorikawa Y, Yamamoto S, Tsuji S, Kamimura N, Ishikawa S, Igarashi H, Makuuchi M, Kokudo N, Sugimura H, *Aburatani H.
  • 雑誌名: Hepatology. 49(2) ページ: 513-22
• [雑誌論文] Anti-glypican 3 antibodies cause ADCC against human hepatocellular carcinoma cells. (2009)
  • 著者名/発表者名: 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.
  • 雑誌名: Biochem Biophys Res Commun. 378(2) ページ: 279-84
• [雑誌論文] Anti-glypican 3 antibody as a potential antitumor agent for human liver cancer. (2008)
  • 著者名/発表者名: 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.
  • 雑誌名: ancer Res. 68(23) ページ: 9832-8
• [雑誌論文] The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. (2008)
  • 著者名/発表者名: Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, Maru Y.
  • 雑誌名: Nat Cell Biol. 10(11) ページ: 1349-55
• [雑誌論文] Human homolog of NOTUM, overexpressed in hepatocellular carcinoma, is regulated transcriptionally by beta-catenin/TCF. (2008)
  • 著者名/発表者名: 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.
  • 雑誌名: Cancer Sci. 99(6) ページ: 1139-46
• [雑誌論文] Constitutive activation of c-Met is correlated with c-Met overexpression and dependent on cell-matrix adhesion in lung adenocarcinoma cell lines. (2008)
  • 著者名/発表者名: Nakamura Y, Matsubara D, Goto A, Ota S, Sachiko O, Ishikawa S, Aburatani H, Miyazawa K, Fukayama M, Niki T.
  • 雑誌名: Cancer Sci. 99(1) ページ: 14-22
• [雑誌論文] Identification of toll-like receptor 3 as a potential therapeutic target in clear cell renal cell carcinoma. (2007)
  • 著者名/発表者名: Morikawa T, Sugiyama A, Kume H, Ota S, Kashima T, Tomita K, Kitamura T, Kodama T, Fukayama M, Aburatani H.
  • 雑誌名: Clin Cancer Res. 13(19) ページ: 5703-9
• [雑誌論文] High-density oligonucleotide array with sub-kilobase resolution reveals breakpoint information of submicroscopic deletions in nevoid basal cell carcinoma syndrome. (2007)
  • 著者名/発表者名: 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.
  • 雑誌名: Hum Genet. 122(5) ページ: 459-66
• [雑誌論文] Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. (2007)
  • 著者名/発表者名: 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.
  • 雑誌名: Nature. 448(7153) ページ: 561-6
• [雑誌論文] Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis. (2007)
  • 著者名/発表者名: Takayama K, Kaneshiro K, Tsutsumi S, Horie-Inoue K, Ikeda K, Urano T, Ijichi N, Ouchi Y, Shirahige K, Aburatani H, Inoue S.
  • 雑誌名: Oncogene. 26(30) ページ: 4453-63
• [雑誌論文] Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. (2006)
  • 著者名/発表者名: Hiratsuka S, Watanabe A, Aburatani H, Maru Y.
  • 雑誌名: Nat Cell Biol. 8(12) ページ: 1369-75
• [雑誌論文] Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein-producing gastric carcinoma. (2006)
  • 著者名/発表者名: Hishinuma M, Ohashi KI, Yamauchi N, Kashima T, Uozaki H, Ota S, Kodama T, Aburatani H, Fukayama M.
  • 雑誌名: Histopathology. 49(5) ページ: 479-86
• [雑誌論文] Oncofetal protein glypican-3 in testicular germ-cell tumor. (2006)
  • 著者名/発表者名: Ota S, Hishinuma M, Yamauchi N, Goto A, Morikawa T, Fujimura T, Kitamura T, Kodama T, Aburatani H, Fukayama M.
  • 雑誌名: Virchows Arch. 449(3) ページ: 308-14
• [雑誌論文] Copy number variation: New insights in genome diversity. (2006)
  • 著者名/発表者名: 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.
  • 雑誌名: Genome Res. 16(8) ページ: 949-61
• [雑誌論文] Noise Reduction from genotyping microarrays using probe level information. (2006)
  • 著者名/発表者名: Komura D, Nishimura K, Ishikawa S, Panda B, Huang J, Nakamura H, Ihara S, Hirose M, Jones KW, Aburatani H.
  • 雑誌名: In Silico Biol. 6(1-2) ページ: 79-92
• [雑誌論文] Molecular karyotyping of human hepatocellular carcinoma using single-nucleotide polymorphism arrays. (2006)
  • 著者名/発表者名: Midorikawa Y, Yamamoto S, Ishikawa S, Kamimura N, Igarashi H, Sugimura H, Makuuchi M, Aburatani H.
  • 雑誌名: Oncogene. 25(40) ページ: 5581-90
• [雑誌論文] Identification of ROBO1 as a Novel Hepatocellular Carcinoma Antigen and a Potential Therapeutic and Diagnostic Target. (2006)
  • 著者名/発表者名: 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.
  • 雑誌名: Clin Cancer Res. 12(11) ページ: 3257-64
• [雑誌論文] 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)
  • 著者名/発表者名: Goto Y, Matsuzaki Y, Kurihara S, Shimizu A, Okada T, Yamamoto K, Murata H, Takata M, Aburatani H, Hoon DS, Saida T, Kawakami Y.
  • 雑誌名: Cancer Res. 66(8) ページ: 4443-9
• [雑誌論文] Hepatocellular carcinoma in Txnip-deficient mice. (2006)
  • 著者名/発表者名: Sheth SS, Bodnar JS, Ghazalpour A, Thipphavong CK, Tsutsumi S, Tward AD, Demant P, Kodama T, Aburatani H, Lusis AJ.
  • 雑誌名: Oncogene. 25(25) ページ: 3528-36
• [雑誌論文] CARAT: A novel method for allelic detection of DNA copy number changes using high density oligonucleotide arrays. (2006)
  • 著者名/発表者名: Huang J, Wei W, Chen J, Zhang J, Liu G, Di X, Mei R, Ishikawa S, Aburatani H, Jones KW, Shapero MH.
  • 雑誌名: BMC Bioinformatics. 7(1) ページ: 83
• [雑誌論文] Chromosomal Numerical Abnormality Profiles of Gastrointestinal Stromal Tumors. (2006)
  • 著者名/発表者名: Yamashita K, Igarashi H, Kitayama Y, Ozawa T, Kiyose S, Konno H, Kazui T, Ishikawa S, Aburatani H, Tanioka F, Suzuki M, Sugimura H.
  • 雑誌名: Jpn J Clin Oncol. 36(2) ページ: 85-92
• [雑誌論文] Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer. (2006)
  • 著者名/発表者名: 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.
  • 雑誌名: J Pathol. 208(5) ページ: 662-672
• [雑誌論文] Elevated expression and potential roles of human Sp5, a member of Sp transcription factor family, in human cancers. (2006)
  • 著者名/発表者名: Chen Y, Guo Y, Ge X, Itoh H, Watanabe A, Fujiwara T, Kodama T, Aburatani H.
  • 雑誌名: Biochem Biophys Res Commun. 340(3) ページ: 758-66
• [雑誌論文] Topological and functional discovery in a gene coexpression meta-network of gastric cancer. (2006)
  • 著者名/発表者名: 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.
  • 雑誌名: Cancer Res. 66(1) ページ: 232-41
• [雑誌論文] Differential expression of S100A2 and S100A4 in lung adenocarcinomas: Clinicopathological significance, relationship to p53 and identification of their target genes. (2005)
  • 著者名/発表者名: 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.
  • 雑誌名: Cancer Sci. 96(12) ページ: 844-57
• [雑誌論文] Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization. (2005)
  • 著者名/発表者名: 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.
  • 雑誌名: Oncogene. 24(47) ページ: 7105-13
• [雑誌論文] Allelic dosage analysis with genotyping microarrays. (2005)
  • 著者名/発表者名: Ishikawa S, Komura D, Tsuji S, Nishimura K, Yamamoto S, Panda B, Huang J, Fukayama M, Jones KW, Aburatani H.
  • 雑誌名: Biochem Biophys Res Commun. 333(4) ページ: 1309-1314
• [雑誌論文] Functional antagonism between Helicobacter pylori CagA and vacuolating toxin VacA in control of the NFAT signaling pathway in gastric epithelial cells. (2005)
  • 著者名/発表者名: Yokoyama K, Higashi H, Ishikawa S, Fujii Y, Kondo S, Kato H, Azuma T, Wada A, Hirayama T, Aburatani H, Hatakeyama M.
  • 雑誌名: Proc Natl Acad Sci U S A. 102(27) ページ: 9661-6
• [雑誌論文] Interpreting expression profiles of cancers by genome-wide survey of breadth-of-expression in normal tissues. (2005)
  • 著者名/発表者名: Ge X, Yamamoto S, Tsutsumi S, Midorikawa Y, Ihara S, Wang SM, Aburatani H.
  • 雑誌名: Genomics 86(2) ページ: 127-141
• [雑誌論文] The Glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. (2005)
  • 著者名/発表者名: 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.
  • 雑誌名: Modern Pathology 18(12) ページ: 1591-8
• [雑誌論文] Overexpression of MUC13 is associated with intestinal-type gastric cancer. (2005)
  • 著者名/発表者名: 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.
  • 雑誌名: Cancer Sci. 96(5) ページ: 265-73
• [雑誌論文] Paired-like homeoprotein ESXR1 acts as a sequence-specific transcriptional repressor of the human K-ras gene. (2005)
  • 著者名/発表者名: Yanagihara M, Ishikawa S, Naito M, Nakajima J, Aburatani H, Hatakeyama M.
  • 雑誌名: Oncogene 24(38) ページ: 5878-87
• [学会発表] Epigenetic dynamics. (2009)
  • 学会等名: 2009 International Conference on Genomics -Human and Beyond
  • 発表場所: henzhen, China
  • 年月日: 20091103-20091105
• [学会発表] Integrated analysis of genomic, epigenomic alterations in liver cancer. (2009)
  • 学会等名: Personal genomes
  • 発表場所: Cold Spring Harbor
  • 年月日: 20090914-20090917
• [学会発表] Cancer genome, epigenome. (2009)
  • 学会等名: HGM2007 Workshop : Cancer Genomics
  • 発表場所: Montreal
  • 年月日: 20090521-20090524
• [学会発表] Epigenomic profiling of cancer. (2009)
  • 学会等名: Epigenetics in Development and Diseases Conference : 4th Asian Epigenomics Meeting
  • 発表場所: Singapore
  • 年月日: 2009-08-25
• [学会発表] Regulatory genomics : allelic variaion in transcriptional variation. (2008)
  • 学会等名: JST-ETH Zurich workshop on Medical Research
  • 発表場所: Zurich
  • 年月日: 20080915-20080916
• [学会発表] Epigenomic profiling : Global DNA methylation profiles in differentiation from ES cells. (2008)
  • 学会等名: 7th Human Genome Organization (HUGO)-Pacific meeting
  • 発表場所: Cebu
  • 年月日: 2008-04-02
• [学会発表] Genomic, epigenomic profiling in cancer. (2007)
  • 学会等名: AACR Centennial Conference Concurrent session : Systems Medicine
  • 発表場所: Singapore
  • 年月日: 20071104-20071108
• [学会発表] エピゲノム解析 (2007)
  • 学会等名: 第66回日本癌学会総会シンポジウム
  • 発表場所: 横浜
  • 年月日: 2007-10-05
• [学会発表] Copy number variation in human genome. (2007)
  • 学会等名: AACR Annual Meeting 2007 Method Workshop‘Interpreting Chromosomal Copy Number Aberrations'
  • 発表場所: Los Angeles
  • 年月日: 2007-04-14
• [学会発表] アレイを用いた網羅的エピゲノム解析 (2006)
  • 学会等名: 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」
  • 発表場所: 横浜
  • 年月日: 2006-09-30
• [学会発表] Glypican-3 as a novel diagnostic, therapeutic target for hepatocellular carcinoma. (2006)
  • 学会等名: Gordon Research Conference (Proteoglycans)
  • 発表場所: 米国
  • 年月日: 2006-07-14
• [備考]
  • URL: http://www.genome.rcast.u-tokyo.ac.jp/
• [産業財産権] 抗Desmoglein3抗体を用いる癌の診断および治療 (2007)
  • 発明者名: 川合重人、中野清孝、伊藤浩孝、油谷浩幸、石川俊平
  • 権利者名: 東京大学、未来創薬研究所
  • 産業財産権番号: 特許権特願2007-19108
  • 出願年月日: 2007-01-30
• [産業財産権] 遺伝子コピーの解析方法及び装置 (2005)
  • 発明者名: 油谷浩幸、石川俊平、西村邦裕、河村大輔
  • 権利者名: 国立大学法人東京大学
  • 産業財産権番号: 特許権PCT/JP2005/16451
  • 出願年月日: 2005-09-07