{"id":36833,"date":"2022-12-07T00:00:54","date_gmt":"2022-12-07T08:00:54","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&#038;p=36833"},"modified":"2024-01-30T14:19:19","modified_gmt":"2024-01-30T22:19:19","slug":"flipping-the-switch-salk-scientists-shed-new-light-on-genetic-changes-that-turn-on-cancer-genes","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/flipping-the-switch-salk-scientists-shed-new-light-on-genetic-changes-that-turn-on-cancer-genes\/","title":{"rendered":"Activando el interruptor: cient\u00edficos de Salk arrojan nueva luz sobre los cambios gen\u00e9ticos que \u201cencienden\u201d genes cancerosos"},"content":{"rendered":"<p>LA JOLLA\u2014Cancer, caused by abnormal overgrowth of cells, is the second-leading cause of death in the world. Researchers from the Salk Institute have zeroed in on specific mechanisms that activate oncogenes, which are altered genes that can cause normal cells to become cancer cells.<\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-12 col-md-push-0\"><div class=\"video-anchor\" id=\"video-RD-pTBv8WIE\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/RD-pTBv8WIE?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>Cancer can be caused by genetic mutations, yet the impact of specific types such as structural variants that break and rejoin DNA, can vary widely. The findings, published in <a href=\"https:\/\/www.nature.com\/articles\/s41586-022-05504-4\" target=\"_blank\" rel=\"noopener\"><em>Naturaleza<\/em><\/a> on December 7, 2022, show that the activity of those mutations depends on the distance between a particular gene and the sequences that regulate the gene, as well as on the level of activity of the regulatory sequences involved.<\/p>\n<figure id=\"attachment_36836\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"300\" class=\"img-responsive wp-image-36836 size-medium\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-300x300.jpg\" alt=\"When genetic mutations cause chromosomes to break apart and fuse together in different ways, normal cells can become cancerous. In this image, normal chromosomes (blue) are shown with chromosomes (green and red) that have been altered using CRISPR-Cas9 genome engineering and fused back together.&lt;br&gt;&lt;br&gt; &lt;a href=&quot;http:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image.jpg&quot;&gt;Click here&lt;\/a&gt; for a high-resolution image.&lt;br&gt;&lt;br&gt; Credit: Salk Institute\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-300x300.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-150x150.jpg 150w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-768x768.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-767x767.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-147x147.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-458x458.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-585x585.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-553x553.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-750x750.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-400x400.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image-200x200.jpg 200w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image.jpg 801w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption class=\"wp-caption-text\">When genetic mutations cause chromosomes to break apart and fuse together in different ways, normal cells can become cancerous. In this image, normal chromosomes (blue) are shown with chromosomes (green and red) that have been altered using CRISPR-Cas9 genome engineering and fused back together.<br \/><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/11\/Dixon-lab-image.jpg\">Haga clic aqu\u00ed<\/a> for a high-resolution image. Credit: Salk Institute<\/figcaption><\/figure>\n<p>This work advances the ability to predict and interpret which genetic mutations found in cancer genomes are causing the disease.<\/p>\n<p>\u201cIf we can better understand why a person has cancer, and what particular genetic mutations are driving it, we can better assess risk and pursue new treatments,\u201d says Salk physician-scientist <a href=\"https:\/\/www.salk.edu\/es\/scientist\/jesse-dixon\/\">Jesse Dixon<\/a>, senior author of the paper and an assistant professor in the Gene Expression Laboratory.<\/p>\n<p>Most genetic mutations have no impact on a cancer and the molecular incidents that lead to oncogene activation are relatively rare. Dixon\u2019s lab studies how genomes are organized in 3D space and seeks to understand why these changes happen in some, but not the majority, of circumstances. The team also wants to identify factors that might distinguish where and when these events occur.<\/p>\n<p>\u201cA gene is like a light and what regulates it are like the light switches,\u201d says Dixon. \u201cWe are seeing that, because of structural variants in cancer genomes, there are a lot of switches that can potentially turn \u2018on\u2019 a particular gene.\u201d<\/p>\n<p>Using CRISPR-Cas9 gene editing, the research team introduced genetic mutations by cutting DNA in certain locations of the genome. They found that some of the variants they created had major impacts on the expression of nearby genes, and could ultimately cause cancer, but that most had essentially no impact. Some genes appeared to go haywire when they were brought into environments with novel regulatory sequences, and others were not affected at all. The type of sequence that was introduced appeared to have a huge impact on whether or not the cell became cancerous.<\/p>\n<figure id=\"attachment_37153\"  class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" width=\"300\" height=\"200\" class=\"img-responsive wp-image-37153 size-medium\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-300x200.jpg\" alt=\"From left: Zhichao Xu and Jesse Dixon\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-300x200.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-1024x683.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-768x512.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-147x98.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-458x305.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-585x390.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-553x369.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-750x500.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-767x511.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-945x630.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-1250x833.jpg 1250w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500-400x267.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500.jpg 1500w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><figcaption class=\"wp-caption-text\">From left: Zhichao Xu and Jesse Dixon <a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2022\/12\/Dixon-PR-1500.jpg\">Haga clic aqu\u00ed<\/a> para obtener una imagen en alta resoluci\u00f3n.<br \/>Cr\u00e9dito: Instituto Salk<\/figcaption><\/figure>\n<p>\u201cOur next move is to test whether there are other factors in the genome that contribute to the activation of oncogenes,\u201d says Zhichao Xu, a postdoctoral fellow at Salk and the paper\u2019s co-first author. \u201cWe are also excited about a new CRISPR genome editing technology we are developing to make this type of genome engineering work much more efficient.\u201d<\/p>\n<p>Other authors on the study are Sahaana Chandran, Victoria T. Le, Rosalind Bump, Jean Yasis, Sofia Dallarda, Samantha Marcotte, Benjamin Clock, Nicholas Haghani, Chae Yun Cho, Selene Tyndale, Graham McVicker, and Geoffrey M. Wahl of Salk; Dong-Sung Lee of the University of Seoul, South Korea; and Kadir Akdemir and P. Andrew Futreal of the University of Texas MD Anderson Cancer Center.<\/p>\n<p>The research was supported by the National Institutes of Health (DP5OD023071), the Leona M. and Harry B. Helmsley Charitable Trust (2017-PG-MED001), the National Institutes of Health National Cancer Institute (R35 CA197687), and the Breast Cancer Research Foundation.<\/p>","protected":false},"featured_media":36836,"template":"","faculty":[378],"disease-research":[46,333],"class_list":["post-36833","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-jesse-dixon","disease-research-cancer-biology","disease-research-genetics"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Flipping the switch: Salk scientists shed new light on genetic changes that turn \u201con\u201d cancer genes - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/flipping-the-switch-salk-scientists-shed-new-light-on-genetic-changes-that-turn-on-cancer-genes\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Flipping the switch: Salk scientists shed new light on genetic changes that turn \u201con\u201d cancer genes - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Cancer, caused by abnormal overgrowth of cells, is the second-leading cause of death in the world. 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Le, Rosalind Bump, Jean Yasis, Sofia Dallarda, Samantha Marcotte, Benjamin Clock, Nicholas Haghani, Chae Yun Cho, Kadir Akdemir, Selene Tyndale, P. Andrew Futreal, Graham McVicker, Geoffrey M. Wahl, and Jesse R. 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