{"49840":{"#nid":"49840","#data":{"type":"news","title":"Rules for Gene Silencing in Cancer Cells Identified","body":[{"value":"\u003Cp\u003EHuman cancers from breast and lung have a common pattern of genes vulnerable to silencing by DNA methylation, researchers at Emory University and the Georgia Institute of Technology have found. The results are published in the January issue of \u003Cem\u003ECancer Research\u003C\/em\u003E.\u003C\/p\u003E\n\u003Cp\u003EOn their way to becoming tumors, cells have to somehow inactivate several \u0022tumor suppressor\u0022 genes that usually prevent cancer formation. Methylation is a subtle punctuation-like modification of the DNA that marks genes for silencing, meaning that they are inactive and don\u0027t make RNA or proteins.\n\u003C\/p\u003E\n\u003Cp\u003E\u0022We\u0027ve developed a set of guidelines that allow us to predict which genes have an increased risk of silencing by DNA methylation,\u0022 says senior author Paula Vertino, PhD, associate professor of radiation oncology at Emory University School of Medicine and Emory Winship Cancer Institute. \u0022That vulnerability could make those genes good markers for diagnosis and risk assessment in patients.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EThe \u0022signature\u0022 of DNA methylation found in cancer cells came from the team\u0027s previous work analyzing cell lines that artificially overproduce an enzyme which adds methylation markers to DNA. Vertino\u0027s team calls the signature PatMAn for \u0022pattern-based methylation analysis.\u0022\u003C\/p\u003E\n\u003Cp\u003EDr. Eva Lee, associate professor and director of Center for Operations Research in Medicine and Healthcare of industrial and systems engineering at Georgia Tech developed the pattern recognition algorithm, feature selection, and predictive tools that pinpointed a small subset of DNA sequence signatures capable of classifying the methylation status.\n\u003C\/p\u003E\n\u003Cp\u003EIn particular, Lee\u0027s approach identified PatMAn, which is based on seven \u0022key words\u0022, 8-10 nucleotides long, that can predict which genes become methylated in breast and lung cancers in addition to artificial cell lines. Postdoctoral fellow Michael McCabe, PhD, took Lee\u0027s predictions and validated their status in the laboratory.\n\u003C\/p\u003E\n\u003Cp\u003EIf the key words are in the DNA sequence near the promoter of the gene, it is more likely to be methylated. The promoter of a gene is the place where enzymes start making DNA into RNA.\u003Cbr \/\u003E\nFurther analysis led to the team\u0027s realization that PatMAn overlaps with the pattern of DNA bound by a set of proteins known as the Polycomb complex in embryonic stem cells. Polycomb appears to keep genes that regulate early development turned off in embryonic stem cells.\u003Cbr \/\u003E\nThe researchers combined PatMAn with the Polycomb binding pattern to generate SUPER-PatMAn, an improved version of PatMAn that could predict methylation-prone genes in cancers with more than 80 percent accuracy.\n\u003C\/p\u003E\n\u003Cp\u003EVertino notes that the methylation pattern in cancer cells appears to echo Polycomb\u0027s binding in embryonic stem cells. Many of the genes affected play important roles in embryonic development.\u003C\/p\u003E\n\u003Cp\u003E\u0022Many of the genes predicted by Lee\u0027s algorithms to be methylation-prone are developmental regulators,\u0022 she says. \u0022Our findings could support the idea that methylation-mediated silencing helps to lock the developmental state of tumor cells into being more stem cell-like.\u0022\n\u003C\/p\u003E\n\u003Cp\u003EAmong cancer biologists, hypermethylation is now the most well characterized epigenetic change to occur in tumors. Lee\u0027s pattern recognition and classification tools offer the opportunity to classify the more than 29,000 known (but as yet unclassified) CpG islands in human chromosomes. This will provide an important resource for the identification of novel gene targets for further study as potential molecular markers that could have an impact on both cancer prevention and treatment. For aggressive cancers such as pancreatic cancer or some forms of incurable brain tumor, the ability to identify such sites offers potential new therapeutic interventions, leading to improved treatment. \n\u003C\/p\u003E\n\u003Cp\u003EThe research was funded by the National Institutes of Health, the National Science Foundation, the American Cancer Society and the Georgia Cancer Coalition.\n\u003C\/p\u003E\n\u003Cp\u003EReference: A multi-factorial signature of DNA sequence and Polycomb binding predicts aberrant CpG island methylation. McCabe, M.T., Lee, E.K, and Vertino, P.M, Cancer Research, 69(1): 282-291, 2009.\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":"","field_summary":[{"value":"Human cancers from breast and lung have a common pattern of genes vulnerable to silencing by DNA methylation, researchers at Emory University and the Georgia Institute of Technology have found. The results are published in the January issue of \u003Cem\u003ECancer Research\u003C\/em\u003E.","format":"limited_html"}],"field_summary_sentence":[{"value":"Rules for Gene Silencing in Cancer Cells Identified"}],"uid":"27279","created_gmt":"2009-04-01 00:00:00","changed_gmt":"2016-10-08 03:03:59","author":"Barbara Christopher","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2009-04-01T00:00:00-04:00","iso_date":"2009-04-01T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"49841":{"id":"49841","type":"image","title":"Professor Eva Lee","body":null,"created":"1449175373","gmt_created":"2015-12-03 20:42:53","changed":"1475894451","gmt_changed":"2016-10-08 02:40:51","alt":"Professor Eva Lee","file":{"fid":"127007","name":"txe87354.jpg","image_path":"\/sites\/default\/files\/images\/txe87354_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/txe87354_0.jpg","mime":"image\/jpeg","size":58268,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/txe87354_0.jpg?itok=ug_jE04x"}},"49842":{"id":"49842","type":"image","title":"Two human chromosomes showing the predicted methyl","body":null,"created":"1449175373","gmt_created":"2015-12-03 20:42:53","changed":"1475894451","gmt_changed":"2016-10-08 02:40:51","alt":"Two human chromosomes showing the predicted methyl","file":{"fid":"127006","name":"tkl87354.jpg","image_path":"\/sites\/default\/files\/images\/tkl87354_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/tkl87354_0.jpg","mime":"image\/jpeg","size":32839,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/tkl87354_0.jpg?itok=5vbfBCKP"}},"49843":{"id":"49843","type":"image","title":"This chart shows the lung tumor methylation agains","body":null,"created":"1449175373","gmt_created":"2015-12-03 20:42:53","changed":"1475894451","gmt_changed":"2016-10-08 02:40:51","alt":"This chart shows the lung tumor methylation agains","file":{"fid":"127005","name":"tqg87301.jpg","image_path":"\/sites\/default\/files\/images\/tqg87301_0.jpg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/tqg87301_0.jpg","mime":"image\/jpeg","size":40764,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/tqg87301_0.jpg?itok=RFYORDJY"}}},"media_ids":["49841","49842","49843"],"groups":[{"id":"1242","name":"School of Industrial and Systems Engineering (ISYE)"}],"categories":[{"id":"129","name":"Institute and Campus"},{"id":"132","name":"Institute Leadership"},{"id":"134","name":"Student and Faculty"},{"id":"135","name":"Research"}],"keywords":[{"id":"385","name":"cancer"},{"id":"1041","name":"dna"},{"id":"247","name":"Emory"},{"id":"1043","name":"eva lee"},{"id":"1042","name":"gene silencing"},{"id":"109","name":"Georgia Tech"}],"core_research_areas":[],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cstrong\u003EBarbara Christopher\u003C\/strong\u003E\u003Cbr \/\u003EIndustrial and Systems Engineering\u003Cbr \/\u003E\u003Ca href=\u0022http:\/\/www.gatech.edu\/contact\/index.html?id=bt3\u0022\u003EContact Barbara Christopher\u003C\/a\u003E\u003Cbr \/\u003E\u003Cstrong\u003E404.385.3102\u003C\/strong\u003E","format":"limited_html"}],"email":["bchristopher@isye.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}