{"id":864,"date":"2016-06-15T14:06:44","date_gmt":"2016-06-15T14:06:44","guid":{"rendered":"https:\/\/neuroepic.mcdb.lsa.umich.edu\/wp\/?page_id=864"},"modified":"2023-04-07T17:47:11","modified_gmt":"2023-04-07T17:47:11","slug":"34-brain-tumors-and-epigenetics","status":"publish","type":"page","link":"https:\/\/courses.lsa.umich.edu\/neuroepic\/34-brain-tumors-and-epigenetics\/","title":{"rendered":"Epigenetics and Brain Tumors"},"content":{"rendered":"\n<p class=\"has-text-align-center wp-block-paragraph\">Elizabeth Le &#8217;20 and Leo Thompson &#8217;20<\/p>\n\n\n\n<figure class=\"wp-block-embed is-type-rich is-provider-spotify wp-block-embed-spotify wp-embed-aspect-21-9 wp-has-aspect-ratio\"><div class=\"wp-block-embed__wrapper\">\n<iframe title=\"Spotify Embed: 33. Epigenetics and Brain Tumors\" style=\"border-radius: 12px\" width=\"100%\" height=\"152\" frameborder=\"0\" allowfullscreen allow=\"autoplay; clipboard-write; encrypted-media; fullscreen; picture-in-picture\" loading=\"lazy\" src=\"https:\/\/open.spotify.com\/embed\/episode\/7FSvrRMjc30yP3eDXwga3f?si=314727addde8493c&#038;utm_source=oembed\"><\/iframe>\n<\/div><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\" \/>\n\n\n\n<p class=\"wp-block-paragraph\">Do cell phones cause brain cancer? What about hair dyes? These are things we use every day\u2014what if they are responsible? So far, studies have found no consistent links<sup>1,2<\/sup>. It might also worry us if we have relatives who have brain cancer because we might think we are likely to have it too. But genetics isn\u2019t everything. For example, glioblastoma, one of the most aggressive forms of brain cancer, is mostly sporadic: it is random who gets it and who doesn\u2019t. However, we aren\u2019t totally doomed, as a lot of research is being done to understand the causes of brain cancer and its potential treatments.<\/p>\n\n\n<p><iframe loading=\"lazy\" title=\"2-Minute Neuroscience: Brain tumors\" width=\"900\" height=\"506\" src=\"https:\/\/www.youtube.com\/embed\/pBSncknENRc?feature=oembed\" frameborder=\"0\" allow=\"accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture; web-share\" allowfullscreen><\/iframe><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Gliomas are brain or spinal cord tumors that originate in glial cells, whose normal function is to support neurons. For example, glial cells insulate neurons and bring them nutrients. When a glial cell is mutated in some way, this leads to abnormal cell growth, or cancer. The glial cell starts to get bigger and divides, forming a tumor after many rounds of division. The tumor can invade surrounding tissues and cause pressure inside the skull. This pressure can result in headaches and changes in cognition. In ancient times, people would relieve this intracranial pressure by drilling a hole in the skull, a process called trephination. More modern treatments involve surgery or radiation, but they are still very invasive and can be dangerous. Clearly, we need to find better treatments. But in order to do so, we must first understand what causes the glial cell to start dividing uncontrollably and how it maintains that growth.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">We can begin by looking at the genome and the epigenome of the glial cell. The genome refers to all of an organism\u2019s genes. Genes are segments of DNA that contain cellular information. This information may be the instructions for making molecular machinery, such as proteins. The genome contains a lot of genes\u2014over 25,000! Although all cells in the human body have the same genes, they may have completely different appearances and functions (e.g., skin vs. muscle cell). These differences result from each cell turning on only specific genes. But there must be a way for cells to control how cells turn on different genes\u2014this is one of the jobs of the epigenome.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">The epigenome refers to the information stored outside of DNA that tells the cell which genes should be turned on and under which conditions. Epigenetic marks are made directly on DNA or DNA packaging proteins known as histones. Histones can be marked to make it easier or harder for molecular machinery to access a gene and turn it on. Think of the histone mark like the conductor of an orchestra: they tell the orchestra which song to play and how loudly or quietly (Figure 1). There are a few different ways that histones can be marked. These include histone methylation and acetylation. Histone marks can either activate (turn on) or silence (turn off) a gene depending on the location and type of mark. When a silencing mark is placed on the histone, less of the gene product is made, similar to how the conductor tells the orchestra to stop playing music or to play quietly. On the other hand, when an activating mark is placed on the histone, more gene product is made, similar to how the conductor tells the orchestra to start playing music or to play loudly. The conductor does not change how the song is written but, rather, how it is performed just like how histone marks do not change the information actually encoded in genes.<\/p>\n\n\n<div class=\"wp-block-image\">\n<figure class=\"aligncenter\"><img loading=\"lazy\" decoding=\"async\" width=\"585\" height=\"535\" src=\"https:\/\/neuroepic.mcdb.lsa.umich.edu\/wp\/wp-content\/uploads\/2020\/04\/The_Music_of_Life-1.jpg\" alt=\"\" class=\"wp-image-1014\" srcset=\"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-content\/uploads\/sites\/16\/2020\/04\/The_Music_of_Life-1.jpg 585w, https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-content\/uploads\/sites\/16\/2020\/04\/The_Music_of_Life-1-300x274.jpg 300w\" sizes=\"auto, (max-width: 585px) 100vw, 585px\" \/><\/figure>\n<\/div>\n\n\n<p class=\"wp-block-paragraph\">Histone marks are maintained by enzymes, a type of molecular machine. Mutations in enzymes can lead to inappropriate histone marks. These can contribute to the inappropriate silencing or activation of important genes. When these genes are misregulated, the cell may begin to behave in abnormal ways and eventually become a tumor and a threat to the organism.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">One such gene is called EZH2, which makes a protein that silences other genes by methylating histones. One research team was researching EZH2 and found that in gliomas, cellular levels of EZH2 are increased, which leads to inappropriate growth and division<sup>3<\/sup>. They also found that cancer patients with increased EZH2 don\u2019t live as long<sup>3<\/sup>. How exactly does EZH2 do this? A separate research team at Sanbo Brain Hospital in Beijing, China, was trying to answer this question<sup>4<\/sup>. They discovered that EZH2 methylates a protein that helps tumors survive and grow by creating special cancer cells that can give rise to more cancer cells<sup>4<\/sup>. Even after treatment like surgery, some of these special cancer cells may remain and give rise to another tumor.&nbsp; However, the researchers did not show if EZH2 is a direct cause of this cancer. We only know that EZH2 is part of the process, so we need more research to understand this process completely and how to correct these epigenetic misregulations.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">There are emerging treatments that target another group of epigenome regulators called histone deacetylases. Histone deacetylases, or HDACs, make it harder to access genes and turn them on. These enzymes can be inhibited by drugs, which could help prevent genes from getting turned off when they should be on. These drugs are called HDAC inhibitors. Researchers at the University of Erlangen-Nuremberg in Germany were looking at an HDAC inhibitor that specifically affects tumor cells. The HDAC inhibitor that the researchers were studying led to fewer glutamate transporters in tumor cells<sup>5<\/sup>. They wanted to reduce the number of glutamate transporters because a higher number of them are associated with greater drug resistance<sup>5<\/sup>. The researchers didn\u2019t want to reduce the number of glutamate transporters in <em>all <\/em>brain cells, however, as glutamate transport is important for a lot of functions in the nervous system. If they prevented glutamate transport in healthy brain cells, it would lead to widespread neurological issues. Fortunately, the researchers\u2019 epigenetic-based approach gave them more precision to target the cancer.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Like the case of EZH2, we don\u2019t completely understand the process by which glutamate transporters are reduced. We might expect an increase in glutamate transporters, as HDAC inhibitors typically make it easier to turn on a gene and make proteins from it. Yet, we see the opposite\u2014a decrease in glutamate transporters\u2014so we don\u2019t have the whole story. Maybe the HDAC inhibitor increased levels of another unknown protein, which then caused fewer glutamate transporters to be made. This protein could be another potential drug target if it is identified.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">There are other opportunities like this to discover new treatments for gliomas using epigenetics. It is important to bring light to the scientific exploration necessary to improve treatments for gliomas and brain cancer because brain cancer is a leading cause of childhood death in the United States<sup>6<\/sup>, and cancer in general is a leading cause of death in the world<sup>7<\/sup>.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Medicine is not &#8220;one-size-fits-all,&#8221; and epigenetics can help us make medical treatments more individualized. As we gain a greater understanding of the epigenetic mechanisms underlying brain cancer, we may be able to personalize care so that each patient can receive a treatment that is specific for their epigenome. Patients often have to try several treatment options before they find one that works for them, but if we can create personalized treatments using epigenetics in the first place, we can save patients from unnecessary risks and even prevent relapse.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Researchers work hard on finding treatments every day. As long as research continues, there is hope. Treatment for cancer has come a long way over the years. It wasn\u2019t long ago that a cancer diagnosis seemed hopeless. Given more time, we may continue to find treatments for different types of cancer. Epigenetics might seem like a funny spin on the word genetics, but it is a line of research that can help us understand disease and close in on a cure.<\/p>\n\n\n\n<p class=\"has-text-align-center wp-block-paragraph\"><strong>References<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">1. Bluhm EC, Hoar Zahm S, Fine HA, et al. Personal hair dye use and risks of glioma, meningioma, and acoustic neuroma among adults. <em>Am J Epidemiol<\/em>. 2007 Jan 1; 165(1): 63-71. doi: 10.1093\/aje\/kwk002.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">2. Boice JD, Tarone RE. Cell phones, cancer, and children. <em>J Natl Cancer Inst. <\/em>2011 Aug 17; 103(16): 1211-1213. doi:10.1093\/jnci\/djr285.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">3. Crea F, Hurt EM, Farrar WL. Clinical significance of Polycomb gene expression in brain tumors. <em>Mol Cancer. <\/em>2010 Sep 30; 9(265). doi:10.1186\/1476-4598-9-265.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">4. Liu H, Sun Y, Qi X, et al. EZH2 phosphorylation promotes self-renewal of glioma stem-like cells through NF-\u03baB methylation. <em>Front Oncol. <\/em>2019 Jul 16; 9(641). doi:10.3389\/fonc.2019.00641.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">5. Wolf IM, Fan Z, Rauh M, et al. Histone deacetylases inhibition by SAHA\/Vorinostat normalizes the glioma microenvironment via xCT equilibration. <em>Sci Rep. <\/em>2014 Sep 17<em>; <\/em>4(6226). doi:10.1038\/srep06226.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">6. Cancer in Children and Adolescents. National Cancer Institute website. https:\/\/www.cancer.gov\/types\/childhood-cancers\/child-adolescent-cancers-fact-sheet#how-common-is-cancer-in-children. Accessed April 22, 2020.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">7. Cancer. World Health Organization website. https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/cancer. Accessed April 22, 2020.<\/p>\n\n\n\n<p class=\"has-text-align-center wp-block-paragraph\"><strong>Video Source<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>2-Minute Neuroscience: Brain Tumors.<\/em> https:\/\/www.youtube.com\/watch?v=pBSncknENRc<\/p>\n\n\n\n<p class=\"has-text-align-center wp-block-paragraph\"><strong>Image Source<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Williams SD, Hughes TE, Adler CJ, Brook AH, Townsend GC. Epigenetics: a new frontier in dentistry. <em>Aust Dent J. <\/em>2014 Feb 24; 59(1 Suppl): 23-33. doi:10.1111\/adj.12155.<\/p>\n\n\n\n<p class=\"has-text-align-center wp-block-paragraph\"><strong>Audio Sources<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Phone ringing sound effect: https:\/\/www.youtube.com\/watch?v=_ctIJySaBmc<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Intro\/outro music: https:\/\/www.youtube.com\/watchv=6by8zhaG04Y&amp;list=PLHrzFRhwKO2Lzw TxlOnoQZqd4CUnQj0vG&amp;index=1<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cDUN-DUN-DUN\u201d sound effect: https:\/\/www.youtube.com\/watch?v=cphNpqKpKc4<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">Orchestra music: https:\/\/www.youtube.com\/watch?v=UQ3rRSzgAlc<\/p>\n\n\n\n<p class=\"wp-block-paragraph\">\u201cBA-DUM-TSS\u201d sound effect: https:\/\/www.youtube.com\/watch?v=fRs0OqV4uSc<\/p>\n\n\n\n<p class=\"has-text-align-center wp-block-paragraph\"><strong>Featured Image Source<\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><em>Doctor attentively examines MRI scan patient stock photo 390249514. Shutterstock. (n.d.). Retrieved September 5, 2022, from https:\/\/www.shutterstock.com\/image-photo\/doctor-attentively-examines-mri-scan-patient-390249514<\/em><\/p>\n\n\n\n<div class=\"wp-block-group is-content-justification-space-between is-nowrap is-layout-flex wp-container-core-group-is-layout-f36ac205 wp-block-group-is-layout-flex\">\n\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Elizabeth Le &#8217;20 and Leo Thompson &#8217;20 Do cell phones cause brain cancer? What about hair dyes? These are things we use every day\u2014what if they are responsible? So far, studies have found no consistent links1,2. It might also worry us if we have relatives who have brain cancer because we might think we are&hellip; <a class=\"more-link\" href=\"https:\/\/courses.lsa.umich.edu\/neuroepic\/34-brain-tumors-and-epigenetics\/\">Continue reading <span class=\"screen-reader-text\">Epigenetics and Brain Tumors<\/span><\/a><\/p>\n","protected":false},"author":47,"featured_media":1618,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"footnotes":""},"class_list":["post-864","page","type-page","status-publish","has-post-thumbnail","hentry","entry"],"_links":{"self":[{"href":"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-json\/wp\/v2\/pages\/864","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-json\/wp\/v2\/users\/47"}],"replies":[{"embeddable":true,"href":"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-json\/wp\/v2\/comments?post=864"}],"version-history":[{"count":1,"href":"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-json\/wp\/v2\/pages\/864\/revisions"}],"predecessor-version":[{"id":2722,"href":"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-json\/wp\/v2\/pages\/864\/revisions\/2722"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-json\/wp\/v2\/media\/1618"}],"wp:attachment":[{"href":"https:\/\/courses.lsa.umich.edu\/neuroepic\/wp-json\/wp\/v2\/media?parent=864"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}