Scientists Find DNA Mutations Driving Skin Cancers

Friday, 25 Jan 2013 08:58 PM

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Human DNA that researchers once thought served no purpose may play a crucial role in deadly skin cancers, harboring some of the mutations that first appear in tumors and promote the malignancy’s growth.

Using gene sequencing technology, scientists at the Dana Farber Cancer Institute in Boston found two mutations among 71 percent of melanoma tumors analyzed. The discovery, the first to identify gene mutations in the vast region of DNA that only last year was shown to have a role turning genes on and off, was published Thursday in two studies in the online journal Science Express.

The findings are a result of faster, cheaper technology that can sequence all of a tumor’s DNA in days. They also prove it’s worth searching the whole genome, not just genes containing instructions for proteins, said Levi Garraway, the study’s senior author and assistant professor of medicine at Harvard Medical School and Dana Farber Cancer Institute.

“Historically, people used to call that junk DNA,” Garraway said in a telephone interview. “We actually didn’t believe the finding at first.”

The mutations are located in a part of the DNA that controls whether a gene called TERT, or telomerase reverse transcriptase, is switched on. When activated, the TERT gene can make a cell replicate almost endlessly — a common feature in cancer cells, according to the researchers.

The mutation can be caused by exposure to sunlight, Garraway said.

“These are mutations of exactly the sort that UV damage causes,” he said. “It makes perfect sense that you’d see these in melanoma.”

12,000 Skin Cancer Deaths

Melanomas account for three-quarters of the 12,000 annual deaths from skin cancer in the U.S., according to the American Cancer Society. They often start as moles on the skin with ill- defined borders and can spread to the lymph nodes and other organs, becoming increasingly difficult to treat, according to the U.S. National Institutes of Health.

After discovering the mutation, the researchers hooked a piece of the mutant DNA to another gene that makes a protein. They found that when combined, the mutant DNA increased production of the protein, and presumed it would do the same thing in the TERT genes, potentially causing melanoma.

The genetic mutations may not be limited to melanomas. The researchers said that early evidence suggests they might be common in liver and bladder cancers as well.

Scientists had previously thought that only genes, small pieces of DNA that make up about 1 percent of the genome, have a function. Findings published in September showed that an underlying circuitry exists in which 80 percent of the DNA within each human cell can contribute to disease. The circuitry plays a role turning on and off genetic activity that can lead to health or to illnesses, according to the studies last year.

Copyright 2013 Bloomberg News
     
   
     
   
 

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