ÿþ<!DOCTYPE html PUBLIC "-//W3C//DTD XHTML 1.0 Strict//EN" "http://www.w3.org/TR/xhtml1/DTD/xhtml1-strict.dtd"> <html xmlns="http://www.w3.org/1999/xhtml"> <head> <meta http-equiv="Content-Type" content="text/html; charset=UTF-8" /> <title>CCLG2 - The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression</title> <meta name="Description" content="Murray Matthew, Saini Harpreet, van Dongen Stijn, Palmer Roger, Muralidhar Balaji, Pett Mark, Piipari Matias, Thornton Claire, Nicholson James, Enright Anton, Coleman Nicholas"><link href="../main.css" rel="stylesheet" type="text/css" /> <!--[if IE]> <link href="../ie.css" rel="stylesheet" type="text/css" /> <![endif]--> <script type="text/javascript" src="../js/external.js"></script> <script type="text/javascript" src="../js/sf.js"></script> </head> <body> <div id="hide">NCRI Conference Abstracts</div> <div id="container"> <div id="nav"> <img src="../images/ncri_logo.gif" alt="NCRI Logo" /> <ul> <li><a href='../pages/1.htm' title='Poster Session A'>Poster Session A </a></li> <li><a href='../pages/2.htm' title='Poster Session B'>Poster Session B </a></li> <li><a href='../pages/3.htm' title='Poster Session C'>Poster Session C </a></li> <li><a href='../pages/4.htm' title='Proffered Paper Sessions'>Proffered Paper Sessions</a></li> <li><a href='../pages/5.htm' title='Plenary Speakers'>Plenary Speakers </a></li> <li><a href='../pages/6.htm' title='Symposia'>Symposia </a></li> <li><a href='../pages/7.htm' title='Parallel Sessions'>Parallel Sessions </a></li> <li><a href='../pages/8.htm' title='Clinical Trials Showcase'>Clinical Trials Showcase </a></li> </ul> <form method="get" action="../search.htm" > <p><input name="zoom_query" value="Search..." id="searchText" type="text" /> <input value="" id="searchInput" type="submit" /></p> </form> </div> <div id="header"> </div> <div id="content"> <span class="breadCrumb"><a href='../pages/3.htm' title = 'Poster Session C'>Poster Session C</a> ...<a href='../pages/PosterTue8.htm' title='PosterTue8'>CCLG McElwain Award</a></span> <h1>CCLG2</h1> <h1>The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression</h1> <h2><u>Matthew Murray </u><sup>1</sup>,Harpreet Saini <sup>2</sup>,Stijn van Dongen <sup>2</sup>,Roger Palmer <sup>1</sup>,Balaji Muralidhar <sup>1</sup>,Mark Pett <sup>1</sup>,Matias Piipari <sup>3</sup>,Claire Thornton <sup>4</sup>,James Nicholson <sup>5</sup>,Anton Enright <sup>2</sup>,Nicholas Coleman <sup>1</sup></h2> <h2>MRC Cancer Cell Unit, Cambridge, United Kingdom <sup>1</sup>,EMBL-EBI, Hinxton, Cambridge, United Kingdom <sup>2</sup>,Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom <sup>3</sup>,Department of Pathology, Royal Group of Hospitals Trust, Belfast, United Kingdom <sup>4</sup>,Department of Paediatric Haematology and Oncology, Addenbrooke's Hospital, Cambridge, United Kingdom <sup>5</sup></h2> <p><b>Background</b></p> <p>We hypothesised that differences in microRNA expression profiles contribute to the contrasting natural history and clinical outcome of the two most common types of malignant germ cell tumour (GCT), yolk sac tumours (YSTs) and germinomas.</p> <p><b>Method</b></p> <p>Using Bioconductor/R, we analysed microRNA microarray data for paediatric GCT samples and published qRT-PCR data for adult samples, with adjusted <em>p</em><0.01 significant. We analysed mRNA expression profiles of paediatric and adult malignant GCTs to identify differentially-expressed genes(log<sub>2</sub> fold-change >1.5 and adjusted <i>p</i><0.01). We used the sequence motif analysis environment iMotifs to predict transcription factor (TF) binding to microRNA promoter regions.</p> <p><b>Results</b></p> <p>By direct comparison, we identified microRNAs significantly up-regulated in YSTs (n=29 paediatric, 26 adult, 11 overlapping) or germinomas (n=37 paediatric). By Taqman qRT-PCR we confirmed differential-expression of 15/16 selected microRNAs and further validated six of these (miR-302b,miR-375,miR-200b,miR-200c,miR-122,miR-205) in an independent sample set. The miR-302 cluster, which is over-expressed in all malignant GCTs, showed further over-expression in YSTs versus germinomas, representing six of the top eight microRNAs over-expressed in paediatric YSTs and seven of the top 11 in adult YSTs. We identified 10 TFs consistently over-expressed in YSTs versus germinomas, with linear regression analysis confirming associations between TF and miR-302 cluster expression levels. Using iMotifs, we identified predicted binding sites for four of the 10 TFs (GATA6, GATA3, TCF7L2 and MAF) in the miR-302 cluster promoter region. Finally, we showed that miR-302 family over-expression in YST is likely to be functionally significant, as mRNAs down-regulated in YSTs were enriched for 3 UTR sequences complementary to the common miR-302a~miR-302d seed. Such mRNAs included mediators of key cancer-associated processes, including tumour suppressor genes, apoptosis regulators and TFs.</p> <p><b>Conclusion</b></p> <p>Differential microRNA expression is likely to contribute to the relatively aggressive behaviour of YSTs and may enable future improvements in clinical diagnosis and/or treatment.</p> </div> <div id="footer"> <a class="inst" href="../instructions.html"><img src="../images/intro/instructions2.jpg" alt="Instructions" width="120" height="26" /> </a> <a class="exit" href="../exit.html"><img src="../images/intro/exit2.jpg" alt="Exit" width="120" height="26" /> </a><p class="footer">Abstract CD sponsored by the <i>BJC - Nature Publishing Group</i>.</p> </div> </div> </body> </html>