Development of a novel method for epigenome analysis and application to cancer diagnosis and order made therapy
Project/Area Number |
19390201
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Sapporo Medical University |
Principal Investigator |
TOYOTA Minoru Sapporo Medical University, 医学部, 教授 (70270676)
|
Co-Investigator(Kenkyū-buntansha) |
SUZUKI Hiromu 札幌医科大学, 医学部, 助教 (20381254)
|
Project Period (FY) |
2007 – 2008
|
Project Status |
Completed (Fiscal Year 2008)
|
Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2008: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
|
Keywords | 消化器癌 / DNAメチル化 / エピジェネティクス / 遺伝子診断 / クロマチン / エピゲノム / ヒストンメチル化 / RNA干渉 / オーダーメード医療 / ヒストン / 個別化医療 |
Research Abstract |
消化器癌においてジェネティックな異常に加え、DNAメチル化やヒストン修飾異常などのエピジェネティックな異常が関与する。ゲノム上の多数の遺伝子がエピジェネティックな異常を有すると考えられ、その全貌を明らかにすることは、消化器癌の診断および治療法開発の上で重要である。本研究では、ゲノム網羅的メチル化解析法と多数の検体を定量的に解析する方法の開発を目指す。Methylated CpG island amplification (MCA)法により、メチル化しているCpG islandを効率よく増幅し、大腸癌細胞株から抽出したDNAから作成したMCAアンプリコンをCy5で、正常大腸組織より抽出したDNAから作成したMCAアンプリコンをCy3でラベルし、Agilent社のwhole genome promoter arrayにハイブリダイズすることにより得られたシグナルを解析し、高メチル化している遺伝子を同定した。また、得られた結果を、ゲノムブラウザBLAT上に表示し、クロマチン免疫沈降法(ChIP on ChIP)のデータと比較することにより、DNAメチル化、ヒストンH3リジン4、リジン27のメチル化との統合解析を可能にした。DNMTあるいはDicerを遺伝学的にノックアウトした大腸癌細胞を用いて、MCA microarrayを行い、DNAメチル化およびヒストン修飾のプロファイルを作成した。本研究により開発された新しいエピゲノム法により消化器癌発生の分子機構の解明や、診断や治療の標的遺伝子の同定に有用と考えられる。
|
Report
(3 results)
Research Products
(82 results)
-
[Journal Article] Sensitive and specific detection of early gastric cancer using DNA methylation analysis of gastric washing2009
Author(s)
Watanabe, Y, Kim, HS, Castoro, RJ, Chyng, W, Estecio, MR, Kondo, K, Guo, Y, Ahmed, SS, Toyota, M, Itoh, F, Suk, KT, Cho, MY, Shen, L, Jelinek, J and Issa, JP.
-
Journal Title
Gastroenterol, Published on line
Related Report
Peer Reviewed
-
[Journal Article] CHFR, a potent tumor suppressor, downregulates interleukin-8 via inhibition of NF-・B2009
Author(s)
Kashima L, Toyota M, Mita H, Suzuki H, Idogawa M, Ogi K, Sasaki Y, , Tokino T.
-
Journal Title
Related Report
Peer Reviewed
-
[Journal Article] Genomic Screening for Genes Silenced by DNA Methylation Revealed an Association between RASD1 Inactivation and Dexamethasone Resistance in Multiple Myeloma2009
Author(s)
Nojima M, Maruyama R, Yasui H, Suzuki H, Maruyama Y, Tarasawa I, Sasaki Y, Asaoku H, Sakai H, Hayashi T, Mori M, Imai K, Tokino T, Ishida T, Toyota M, Shinomura Y.
-
Journal Title
Clin Cancer Res (in press)
Related Report
Peer Reviewed
-
[Journal Article] Overexpression of Aurora a by loss of CHFR gene expresion increases the growth of HTLV-1-infected T cells through enhanced NF-kB activity2009
Author(s)
Tomita M, Toyota M, Ishikawa C, Nakazato T, Okudaira T, Matsuda T, Uchihara J, Taira N, Ohshiro K, Senba M, Tanaka Y, Ohshima K, Saya H, Tokino T, Mori N.
-
Journal Title
Int J Cancer 124
Pages: 2607-2615
Related Report
Peer Reviewed
-
[Journal Article] p53 family members regulate the expression of the apolipoprotein D gene2009
Author(s)
Sasaki Y, Negishi H, Koyama R, Anbo N, Ohori K, Idogawa M, Mita H, Toyota M, Imai K, Shinomura Y, Tokino T.
-
Journal Title
J Biol Chem 284
Pages: 872-883
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Identification of flotillin-2, a major protein on lipid rafths, as a novel target of the p53 family members2008
Author(s)
Sasaki Y, Ohshima Y, Koyama R, Maruyama R, Akashi H, Mita H, Toyota M, Shinomura Y, Imai K, Tokino T.
-
Journal Title
Mol Cancer Res 6
Pages: 395-406
Related Report
Peer Reviewed
-
[Journal Article] Epigenetic inactivation of RASSF2 in oral squamous cell carcinoma2008
Author(s)
Imai T, Toyota M, Suzuki H, Akino K, Ogi K, Sogabe Y, Kashima L, Maruyama R, Nojima M, Mita H, Sasaki Y, Itoh F, Imai K, Shinomura Y, Hiratsuka H, Tokino T.
-
Journal Title
Cancer Sci 99
Pages: 958-966
NAID
Related Report
Peer Reviewed
-
[Journal Article] Cytoplasmic RASSF2A is a proapoptotic mediator whose expression is epigenetically silenced in gastric cancer2008
Author(s)
Maruyama R, Akino K, Toyota M, Suzuki H, Imai T, Ohe-Toyota M, Yamamoto E, Nojima M, Fujikane T, Sasaki Y, Yamashita T, Watanabe Y, Hiratsuka Y, Hirata K, Itoh F, Imai K, Shinomura Y, Tokino T.
-
Journal Title
Carcinogenesis 29
Pages: 1312-1318
Related Report
Peer Reviewed
-
-
-
[Journal Article] Frequent epigenetic inactivation of SFRP genes in hepatocellular carcinoma2008
Author(s)
Takagi H, Sasaki S, Suzuki H, Toyota M, Maruyama R, Nojima M, Yamamoto H, Omata M, Tokino T, Imai K, Shinomura Y.
-
Journal Title
J. Gastroenterol 43
Pages: 378-389
NAID
Related Report
Peer Reviewed
-
[Journal Article] LINE-1 hypomethylation is associated with increased CpG island methylation in helicobactor pylori-related enlarged fold gastritis2008
Author(s)
Yamamoto E, Toyota M, Suzuki H, Kondo Y, Imai K, Sanomura T, Murayama Y, Ohe-Toyota M, Maruyama R, Nojima M, Ashida M, Fujii K, Sasaki Y, Hayashi N, Mori M, Imai K, Tokino T, Shinomura Y.
-
Journal Title
Cancer Epidemiol Biomarkers Prev 17
Pages: 2555-2564
Related Report
Peer Reviewed
-
-
[Journal Article] Frequent epigenetic inactivation of Wnt antagonist genes in breast cancer2008
Author(s)
Suzuki H, Toyota M, Caraway H, Gabrielson E, Ohmura T, Fujikane T, Nishikawa N, Sogabe Y, Nojima M, Sonoda T, Mori M, Hirata K, Imai K, Shinomura Y, Baylin SB, Tokino T.
-
Journal Title
British J Cancer 98
Pages: 1147-1156
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Integrated genetic and epigenetic analysis identifies colon cancer corresponding to three different subclasses of disease2007
Author(s)
Shen L, Toyota M, Kondo Y, Lin E, Zhang L, Guo Y, Hernandez N, Chen X, Ahmed S, Konishi K, Hamilton SR, Issa JPJ.
-
Journal Title
Proc Natl Acad Sci U S A 104
Pages: 18654-18659
Related Report
Peer Reviewed
-
[Journal Article] Gene amplification and overexpression of PRDM14 in breast cancer2007
Author(s)
Nishikawa N, Toyota M, Suzuki H, Homma. T, Fujikane T, Ohmura T, Nishidate T, Ohe-Toyota M, Maruyama R, Sonoda T, Sasaki Y, Urano T, Imai K, Hirata K, Tokino T.
-
Journal Title
Cancer Res 67
Pages: 9649-9657
Related Report
Peer Reviewed
-
[Journal Article] Comparing the DNA hypermethylation with gene mutations in human colorectal cancer2007
Author(s)
Schuebel KE, Chen E, Cope Lm Glockner SC, Suzuki H, Yi JM, Chan TA, Van Neste L, Van Criekinge W, van den Bosch S, van Engeland M, Ting AH, Jair K, Yu W, Toyota M, Imai K, Ahuja N, Herman JG, Baylin SB.
-
Journal Title
Plos Genet 3
Pages: 1709-1723
Related Report
Peer Reviewed
-
[Journal Article] Identification of DFNA5 as a target of epigenetic inactivation in gastric cancer2007
Author(s)
Akino K, Toyota M, Suzuki H, Imai T, Maruyama R, Kusano M, Nishikawa N, Watanabe Y, Sasaki Y, Abe T, Yamamoto E, Tarasawa I, Sonoda T, Mori M, Imai K, Shinomura Y, Tokino T.
-
Journal Title
Cancer Sci 98
Pages: 88-95
Related Report
Peer Reviewed
-
[Journal Article] Antitumor effect of adenoviras-mediated p53 family gene transfer on osteosarcoma cell lines2007
Author(s)
Ohshima Y, Sasaki Y, Negishi H, Idogawa M, Toyota M, Yamashita T, Wada T, Nagoya S, Kawaguchi S, Yamashita T, Tokino T.
-
Journal Title
Cancer Biol Ther 6
Pages: 1058-1066
Related Report
Peer Reviewed
-
[Journal Article] Frequent epigenetic inactivation of SFRP genes and constitutive activation of Wnt signaling in gastric cancer2007
Author(s)
Nojima M, Suzuki H, Toyota M, Watanabe Y, Maruyama R, Sasaki S, Sasaki Y, Mita H, Nishikawa N, Yamaguchi K, Hirata K, Itoh F, Tokino T, Mori M, Imai K, Shinomura Y.
-
Journal Title
Oncogene 26
Pages: 4699-4713
NAID
Related Report
Peer Reviewed
-
[Journal Article] Expression profiling of PRDM family genes identified PRDM5 as a target of epigenetic silencing in colorectal and gastric cancer2007
Author(s)
Watanabe Y, Toyota M, Kondo Y, Suzuki H, Imai T, Ohe-Toyota M, Maruyama R, Nojima M, Sasaki Y, Sekido Y, Hiratsuka H, Shinomura Y, Imai K, Itoh F, Tokino T.
-
Journal Title
Clin Cancer Res 13
Pages: 4786-4794
Related Report
Peer Reviewed
-
[Journal Article] Frequent epigenetic inactivation of DICKKOPF family genes in human gastrointestinal tumors2007
Author(s)
Sato H, Suzuki H, Toyota M, Nojima M, Maruyama R, Sasaki S, Takagi H, Sogabe Y, Sasaki Y, Idogawa M, Sonoda T, Mori M, Imai K, Tokino T, Shinomura Y.
-
Journal Title
Carcinogenesis 28
Pages: 2459-2466
NAID
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-