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Session 6: Epigenetics Poster 9 Genome-wide DNA methylation Signatures of Cholangiocarcinoma Ruethairat Sriraksa 1,3 , Constanze Zeller 2 , Wei Dai 2 , Afshan Siddiq 4 , Andrew J Walley 5 , Siobhan C McKay 7 , Naoya Kobayashi 6 , Geraldine Thomas 7 , Temduang Limpaiboon 3 , Robert Brown 2 . 1 Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand; r.sriraksa@gmail.com; 2 Epigenetics Unit, Department of Surgery and Oncology, Hammersmith Hospital, Imperial College, Du Cane Road, London W12 0NN, UK; c.zeller@imperial.ac.uk; w.dai@imperial.ac.uk; b.brown@imperial.ac.uk; 3 Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; temduang@kku.ac.th; 4 Department of Epidemiology and Biostatistics, School of Public Health, Burlington- Danes Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK; a.siddiq@imperial.ac.uk; 5 Department of Genomics of Common Disease, School of Public Health, Burlington- Danes Building, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK; a.walley@imperial.ac.uk; 6 Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan; immortal@md.okayamau.ac.jp; 7 Molecular Pathology, Hammersmith Hospital, Imperial College, Du Cane Road, London W12 0NN, UK; siobhan.mckay08@imperial.ac.uk; geraldine.thomas@imperial.ac.uk To address genome-wide DNA methylation changes in cholangiocarcinoma (CCA), we performed genome-wide DNA methylation profiling of 32 primary CCA, 6 matched adjacent normal samples, 5 CCA cell lines and a normal biliary cell line using HumanMethylation27 BeadChips. We identified 718 and 594 CG sites as being hypermethylated and hypomethylated in CCA compared to adjacent normal samples, respectively (False Discovery Rate; FDR85% of primary CCA as compared to adjacent normal samples using bisulfite pyrosequencing. Moreover, detailed gene set enrichment analysis (GSEA) showed overrepresentation of hypermethylated CpG sites associated with homeobox genes, PRC2 targets, EED targets, SUZ12 targets and H3K27 targets. In contrast, hypomethylation of NOS targets and OCT4 targets was significantly enriched in CCA. Epigenetic aberrations of these genes have been proposed to play roles in the stem cell origin of cancers and they might provide new therapeutic targets for CCA. To our knowledge, this is the first report of genome-wide DNA methylation study in cholangiocarcinoma which provides a useful resource of epigenetic signature that could serve as the biomarkers. However, the biological functions and clinical application of these candidate DNA methylation changes should be further clarified. 134
Session 6: Epigenetics Poster 10 Epigenetic regulation of proMMP-1, -2 and -9 expression in HT1080 human fibrosarcoma cell line. M. Poplineau 1 , J. Dufer 1 , F. Antonicelli 1 and A. Trussardi-Regnier 1 . 1 Facultés de Médecine et Pharmacie, Unité MEDyC, UMR CNRS/URCA n°6237 :1, avenue du Maréchal Juin, 51096 REIMS Cedex, France. E-mail address: aurelie.trussardi@univ-reims.fr, frank.antonicelli@univ-reims.fr, jean.dufer@univ-reims.fr, mathilde.poplineau@etudiant.univ-reims.fr. The matrix metalloproteinase (MMP) family members play an important role in various physiological and pathological processes. The collagenase MMP-1 and the gelatinases MMP- 2 and MMP-9 are involved in tumor invasiveness but the regulation of their expression is not fully elucidated and could implicate epigenetic mechanisms (DNA methylation and/or histone posttranslational modifications). The aim of this study was to analyze the effects of the histone deacetylase inhibitor trichostatine A (TSA) and the inhibitor of DNA methylation 5aza-2’-deoxycytidine (5-azadC) on the MMP-1,-2 and -9 expressions in human HT1080 fibrosarcoma cell line. Real time RT-PCR revealed that 5-azadC or 5-azadC + TSA but not TSA alone (despite histone H4 hyperacetylation) increase mRNA levels. This transcription activation is correlated with chromatin decondensation observed by nuclear texture image analysis. Western blot and gelatin zymography analysis of cell culture media revealed significant secretion of proMMP-1 and high activity of MMP-2 and MMP-9, after 5-azadC or 5-azadC + TSA treatment. These results suggest that epigenetic mechanism could be involved in MMP-1, MMP-2, MMP-9 gene and protein expression and could thereby modulate the invasive behavior of tumor cells. 135
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Luxembourg, January 26th to 28th, 2
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Luxembourg, January 26th to 28th, 2
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Preface In 1998, we organized the f
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European Research Institute for Int
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How to reach the congress center? -
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Many thanks to all exhibitors Pleas
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Wednesday January 26th, 2011 8h00 -
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Workshops 2 and Posters Session 2 1
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Oral presentations (In chronologica
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Activated Ras Requires Autophagy to
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DNA-damage stress response in femal
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Towards understanding of life and d
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Systems Analysis of Endocytosis by
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Whole genome scans in drosophila to
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Search for the effects of anticance
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Redox regulation of transcription f
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A dual role of JAK1: regulation of
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Immunity and death in chronic viral
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Study of the anti-apoptotic role of
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Proteomic phenotyping of the cell s
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Traveling to the Ends of the Proteo
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Site-Specific Identification of SUM
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Mechanisms of Epigenetics in Health
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MicroRNAs and erythroid differentia
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A Systems Approach to Modeling and
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Targeting the invasive phenotype us
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Genes related to energy metabolism
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Pathological aspects of vascular ag
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Control of class III PI3 kinase in
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p75NTR regulates A! deposition by i
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Workshop presentations 61
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Agilent Technologies New enrichment
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MAPTrix TM biomimetics from amsbio:
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2 1 Map and bus stops 3 4 Meeting C
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11 5 PARC DE L'EUROPE Dommeldange W
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A heart for cancer sick children To
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Wednesday January 26th Keynote sess
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Session 1: Cell death Poster 1 The
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Session 1: Cell death Poster 3 In v
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Session 1: Cell death Poster 5 Func
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Session 1: Cell death Poster 7 Mode
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Session 1: Cell death Poster 9 Prot
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Session 1: Cell death Poster 11 MAP
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Session 1: Cell death Poster 13 Nit
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Session 1: Cell death Poster 15 �
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Page 103 and 104: Posters are classified by session a
Page 105 and 106: Session 2: Cell signaling Poster 2
Page 117 and 118: Session 3: Transcriptional control
Page 127 and 128: Session 4: Immunology Poster 2 Immu
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Page 131 and 132: Session 4: Immunology Poster 6 Iden
Page 133 and 134: Session 4: Immunology Poster 8 Smal
Page 135 and 136: Session 4: Immunology Poster 10 INJ
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Page 139 and 140: Session 5: Proteomics Poster 1 Phos
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Page 145 and 146: Session 6: Epigenetics Poster 2 Ree
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Page 149 and 150: Session 6: Epigenetics Poster 6 Fun
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Page 157 and 158: Session 7: Cancer signaling network
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Page 195 and 196: Session 9: Neurodegenerative Diseas
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Session 9: Neurodegenerative diseas
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Notes 195
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List of participants (In alphabetic
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Mrs. Emilie Bana Laboratoire d'Ing
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Dr. Alessandro Corsaro Laboratory o
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Pr. Paul Fisher Microbial Cell Biol
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Mr. Kasper Hoebe Cincinnati Childre
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Mr. Hendrik Koopmans Cell Biology W
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Mr. Romuald Menth Technical Support
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Notes 218
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Notes 220
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We thank our sponsors:
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