 Our DNA influences the behavior of our cells. DNA is found in a nucleus and it provides the template for the production of proteins. So a specific DNA sequence makes a specific protein. However, the story is a little bit more complicated because only 1% of the DNA makes protein. So what does the other 99% of the DNA in our cells do? This dark matter, as people used to call it. Is it just junk DNA? Well, it turns out that 99% of our DNA is not useless. It controls when and how much proteins are made by the 1% of the DNA that makes proteins. And thanks to great technical advances, scientists have recently started looking at the entire DNA sequence of patients. Not just the 1% that makes proteins, but 100% of the DNA, all 3 billion DNA base pairs. If you were to read out loud all of the DNA sequence, it would take 9.5 years reading non-stop at a rate of 10 base pairs per second. That's a huge amount of information. Changes in the DNA sequence, which we call mutations, explains the development of one of the biggest killers in the world, cancer. Cancer cells divide uncontrollably to form tumors. This is due to mutations in their DNA sequence. We can visualize the process of cancer development as a staircase, where as cells acquire more and more mutations, they move up this staircase to become cancer. The mutations that allow a cell to move up the staircase are called driver mutations. Because one type of cancer, for example, breast cancer, can take multiple paths and be caused by different DNA mutations, depending on the patient, it's very important for us to understand what is the underlying genetic cause in order to develop targeted therapies. In other words, what are the driver mutations? To find these mutations, scientists had previously been looking mostly for DNA changes in the 1% of the DNA sequence that makes proteins. But the scientists of this paper wanted to shed light on this dark matter to see if there were any driver mutations in the rest of the DNA that doesn't make proteins. Their findings were published in their article titled, Church Promoter Mutations in Familiar and Spratic Melanoma, produced by the Schadendorf and Kumar labs at the German Cancer Research Center in the University Hospital Essen in Science Magazine in February 2013. These scientists studied a large multi-generational family that had a very high incidence of skin cancer or melanoma. Because cancer ran in the family, this suggested that something in the DNA sequence was causing these individuals to develop cancer. So the scientists looked at the entire DNA sequence of individuals in the family with and without cancer. And what they found was a mutation or a change in the DNA sequence in a part of the DNA that doesn't make proteins. This mutation was found in all individuals that had developed cancer, but only present in one individual that didn't develop cancer, but instead had many moles, which increases one's likelihood of developing melanoma. Considering the size of the family, this provides strong evidence that this mutation is responsible for causing cancer in the family. So how could this mutation be involved in causing cancer? Well this mutation is present near a piece of DNA that encodes a protein which makes telomerase. The mutation controls how much telomerase is produced and causes a 2-4 fold increase in the levels of telomerase in cells. To understand what telomerase is and what happens when you have more telomerase, let's step back a little bit and go back to the DNA. DNA is not one long sequence. Instead DNA is organized in 46 chromosomes, which consist of different strands of DNA twisted on themselves. At each end of the DNA sequence is a piece of DNA called a telomere, here in red, which is similar to the plastic sheath at the end of shoelaces that prevent shoelaces from getting too short. As cells divide, the telomere in red gets shorter and shorter. When the telomere gets critically short, the cell can't divide. Similarly, if the plastic sheath on a shoelace is removed, you will eventually no longer be able to tie your shoes. What telomerase does is it lengthens this telomere DNA to allow the cell to keep dividing essentially forever. The telomerase is important to extend life span in normal cells. Before this finding, it was thought that telomerase in cancer cells simply allowed the cells that had reached the top of the staircase to keep dividing, but was not important in driving the cells up the staircase to a cancer state. So how does this finding contribute to this view? As I mentioned, the mutation discovered here increases telomerase levels in cells and was found in a family where every person, except for one, that had the mutation developed cancer and mostly melanoma. So this strongly suggests that this mutation is doing more than just allowing cells that are cancerous to keep dividing. Instead, this suggests that this mutation is actually driving cells one step up the staircase. If these cells acquire more mutations, they will keep moving up the staircase until they become cancerous. So this article makes us rethink the way we see telomerase in cancer development. This is one of the first indications that increasing telomerase alone can drive cells towards becoming cancer. But the scientists also found evidence that this mutation is present in 74% of melanoma patient cell lines that didn't have a family history of melanoma. That's a huge percentage. In those patients, the mutation was caused by UV light damage from sun exposure. Another scientific article that was published at the same time by the Gowerway Laboratory at Harvard Medical School also found this mutation in bladder, liver, kidney, and thyroid cancers. So what did this study show? These scientists identified one of the most common cancer-causing mutations in melanoma, a mutation that increases telomerase and drives cancer development of all sorts of cancers. Although it still remains to be seen exactly how telomerase drives cancer development. Cancer patients with the mutation inherited the mutation from their parents in the familial case or acquired it from sun exposure. So overall, this study showed that it's very important to look at 100% of the DNA sequence because mutations in the 99% of the DNA that doesn't make proteins can be driving cancer. So what does this mean for you? This study identifies a pathway that increases telomerase and that drives tumor development. So it provides new evidence that developing a therapy to block telomerase may be very effective to prevent 75% of melanomas. Because this mutation is a simple change in the DNA sequence, it would be possible to determine if a specific tumor is caused by this mutation and how likely a patient would be to respond to a drug against this pathway. It's surprising that mutations in what was seen as junk DNA can be so common and so important to driving cancer development. So as you can tell, sequencing 100% of patients' DNA in a cost-effective way has and will continue to provide clues as to the cause of many diseases, in this case melanoma. This will be very important as we develop targeted therapies for an individual patient based on his or her genetic makeup. This is where the future of medicine is heading towards precision medicine. This video has been provided to you by Eureka Science. 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