"This new finding represents an initial foray into the 'dark matter' of the cancer genome," said Dr. Levi Garraway, senior author of the study and an assistant professor of medicine at the Dana-Farber Cancer Institute. "In addition, this represents the discovery of two of the most prevalent melanoma gene mutations. Considered as a whole, these two TERT promoter mutations are even more common than BRAF mutations in melanoma. Altogether, this discovery could cause us to think more creatively about the possible benefits of targeting TERT in cancer treatment or prevention."
The study, published this week in the journal Science Express, shows that the two mutations take place in regions of non-coding DNA. Non-coding DNA refers to the large regions of DNA that do not contain genetic instructions for making proteins. Though non-coding DNA makes up 99% of a cell's genome, the information was previously dismissed as meaningless.
The researchers found that the mutations affect affect a promoter region adjacent to the TERT gene, which contains a "recipe" for creating telomerase reverse transcriptase - an enzyme that can make cells "virtually immortal." Promoter regions in DNA control the rate of a gene's transcription. It is presumed that the mutations can kick the TERT gene "into overdrive" and contribute to the development of melanoma.
"We think these mutations in the promoter region are potentially one way the TERT gene can be activated," said Dr. Franklin Huang, co-author of the study.
The mutations were found by analyzing whole-genome data. Huang and his colleagues also found that the same mutations are present in other cancers, and could be common in bladder and liver cancers.