{"428651":{"#nid":"428651","#data":{"type":"news","title":"Cancer may not be caused by mutations alone","body":[{"value":"\u003Cp class=\u0022p1\u0022\u003EThere are more than 200 diseases called cancer and they all start when abnormal cells in a part of the body divide uncontrollably, growing with reckless abandon. Why these bad cells run amok is the focus of thousands of researchers across the world and billions of dollars.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe current consensus among the vast majority of researchers is that most if not all cancers are caused by a change in or damage to genes, collectively called \u201cmutations.\u201d But research from two Georgia Institute of Technology cancer geneticists may alter the prevailing view.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cWith the exception of the few things that we know are related to predisposition, the consensus view now is that cancer is due to \u2018de novo\u2019 mutations,\u201d says John McDonald, professor of Biology and director of the Integrated Cancer Research Center (ICRC) at the Petit Institute for Bioengineering and Bioscience.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe term \u201cmutation\u201d is typically used to encompass a broad spectrum on genomic level lesions ranging from small changes in the single letter DNA code (point mutations) to large chromosomal deletions and rearrangements (structural mutations) that can adversely affect the architecture and function of cells.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe explosion in the number of genome sequencing studies carried out over the past several years comparing normal and cancer tissues has generated an abundance of genome databases ripe for computational analyses of the spectrum of mutations associated with cancer. \u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EIn a study just reported in the online journal \u003Cem\u003E\u003Ca href=\u0022http:\/\/www.biomedcentral.com\/1755-8794\/8\/40\u0022\u003EBMC Medical Genomics \u003C\/a\u003E\u0026nbsp;\u003C\/em\u003EMcDonald and Vinay Mittal (former graduate student in McDonald\u2019s lab, now a bioinformatics scientist with Thermo Fisher Scientific in Michigan) report the results of a detailed analysis of structural mutations associated with ovarian cancer \u2013 the deadliest of all gynecological cancers.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EUnlike most computational analyses of cancer mutations, the authors not only analyzed the structural variants found in cancer tissues but also those naturally occurring mutations present in the normal tissues of the same patients.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cThe results were remarkable in the shear number of structural mutations identified,\u201d says McDonald. They found 4,516 structural mutations in the cancer tissues and 5,518 in the normal tissues.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cMost of the structural variants identified are probably of little functional significance,\u201d says Mittal. \u201cBut around 10 percent of the variants identified are \u2018gene-fusions\u2019 with the potential to generate hybrid proteins that may contribute significantly to cancer onset and progression.\u201d\u003C\/p\u003E\u003Ch6 class=\u0022p1\u0022\u003E\u003Cstrong\u003EDisease of Misinformation\u003C\/strong\u003E\u003C\/h6\u003E\u003Cp class=\u0022p1\u0022\u003EIn addition to identifying and categorizing all of the structural variants associated with the ovarian cancer patients, Mittal and McDonald went on to determine the extent to which these variants were actually being expressed in the normal and cancer tissues.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EWhile our DNA harbors all of the genetic information in our cells, like a blueprint, not all of this information is transmitted or \u201cexpressed\u201d at any given time.\u0026nbsp; Information in DNA must be transmitted to an intermediary RNA molecule before it can result in the manufacture of a functional protein. For example, many of the genes necessary for liver cell function are not expressed in the brain, and vice versa.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe detailed pattern of regulatory controls typical in normal cells is often disrupted in cancer cells. Thus, cancer cells not only contain DNA lesions or mutations not detected in normal cells, they may also display abnormal expression patterns, \u201cgenetic information that is silenced in normal cells but abnormally expressed in cancer cells,\u201d says McDonald, who has called cancer, \u201ca disease of misinformation.\u201d\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003ECells get wrong information, such as being told to rapidly divide when they should be inactive. It could be an error in the cell\u2019s blueprint (a mutation). Or, it could be an error in the flow of information (abnormal expression), a regulation problem, which gets to what may be the most remarkable and unexpected finding of the study, according to McDonald.\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cAt least some of the functionally significant abnormal gene-fusions expressed in the cancer tissues are also present in normal tissues,\u201d he says. \u201cBut they are not being expressed.\u201d\u0026nbsp;\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EThe results of the study underscore the importance of gene regulation in cancer. It raises questions about how and when cancer is due to a de novo mutational event or a mistake in information flow.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u201cThe accumulation of structural variants and other mutations in our cells with the potential to cause cancer may be inevitable as we age, but our cells may naturally strive to suppress the expression of some of this misinformation,\u201d says McDonald. \u201cThis suggests that while mutations may be necessary for the onset of most cancers, they my not be sufficient. We need to better understand the regulatory mechanisms that can suppress cancer causing mutations in some individuals and how these mechanisms break down in cancer patients.\u201d\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003EStudies are currently on-going to see if the suppression of cancer causing genetic lesions extends to other classes of mutation and to understand the molecular processes that may underlie the suppression mechanism. The hope is that this work will lead to novel and more effective therapies and treatments for cancer.\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cem\u003EThe Parker H. Petit Institute for Bioengineering and Bioscience, an internationally recognized hub of multidisciplinary research at the Georgia Institute of Technology, brings engineers, scientists, and clinicians together to solve some of the world\u2019s most complex health challenges. With 17 research centers, more than 170 faculty members, and $24 million in state-of-the-art facilities, the Petit Institute is translating scientific discoveries into game-changing solutions to solve real-world problems.\u003C\/em\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003E\u003Cbr \/\u003E\u003C\/strong\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003ECONTACT:\u003C\/strong\u003E\u003C\/p\u003E\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003E\u003Ca href=\u0022http:\/\/hg.gatech.edu\/node\/jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003C\/strong\u003E\u003Cbr \/\u003ECommunications Officer II\u003Cbr \/\u003EParker H. Petit Institute for\u003Cbr \/\u003EBioengineering and Bioscience\u003C\/p\u003E","summary":null,"format":"limited_html"}],"field_subtitle":[{"value":"New research by Georgia Tech scientists underscores importance of gene regulation"}],"field_summary":[{"value":"\u003Cp class=\u0022p1\u0022\u003E\u003Cstrong\u003ENew research by Georgia Tech scientists underscores importance of gene regulation\u0026nbsp;\u003C\/strong\u003E\u003C\/p\u003E","format":"limited_html"}],"field_summary_sentence":[{"value":"New research by Georgia Tech scientists underscores importance of gene regulation"}],"uid":"28153","created_gmt":"2015-07-27 14:38:16","changed_gmt":"2016-10-08 03:19:15","author":"Jerry Grillo","boilerplate_text":"","field_publication":"","field_article_url":"","dateline":{"date":"2015-07-27T00:00:00-04:00","iso_date":"2015-07-27T00:00:00-04:00","tz":"America\/New_York"},"extras":[],"hg_media":{"337561":{"id":"337561","type":"image","title":"John McDonald","body":null,"created":"1449245216","gmt_created":"2015-12-04 16:06:56","changed":"1475895051","gmt_changed":"2016-10-08 02:50:51","alt":"John McDonald","file":{"fid":"200556","name":"timthumb_3.jpeg","image_path":"\/sites\/default\/files\/images\/timthumb_3_0.jpeg","image_full_path":"http:\/\/www.tlwarc.hg.gatech.edu\/\/sites\/default\/files\/images\/timthumb_3_0.jpeg","mime":"image\/jpeg","size":71197,"path_740":"http:\/\/www.tlwarc.hg.gatech.edu\/sites\/default\/files\/styles\/740xx_scale\/public\/images\/timthumb_3_0.jpeg?itok=uYzWBM1i"}}},"media_ids":["337561"],"groups":[{"id":"1292","name":"Parker H. Petit Institute for Bioengineering and Bioscience (IBB)"}],"categories":[],"keywords":[{"id":"280","name":"Cancer research"}],"core_research_areas":[{"id":"39441","name":"Bioengineering and Bioscience"}],"news_room_topics":[],"event_categories":[],"invited_audience":[],"affiliations":[],"classification":[],"areas_of_expertise":[],"news_and_recent_appearances":[],"phone":[],"contact":[{"value":"\u003Cp\u003E\u003Ca href=\u0022http:\/\/hg.gatech.edu\/node\/jerry.grillo@ibb.gatech.edu\u0022\u003EJerry Grillo\u003C\/a\u003E\u003Cbr \/\u003ECommunications Officer II\u003Cbr \/\u003EParker H. Petit Institute for\u003Cbr \/\u003EBioengineering and Bioscience\u003C\/p\u003E","format":"limited_html"}],"email":["jerry.grillo@ibb.gatech.edu"],"slides":[],"orientation":[],"userdata":""}}}