New DNA Mutations Discovered in Malignant Melanomas

The mutations, which may be the most common in melanoma cells, share genetic hallmarks with other ultraviolet light–induced mutations. Researchers at the Dana-Farber Cancer Institute and the Broad Institute of Harvard and MIT have found new genetic mutations that appear in a combined total of 71% of malignant melanomas. They reported their findings in the February 22, 2013, edition of Science.

 The mutations were found in the “dark matter” of the tumor—sometimes referred to as “junk” DNA—because this area does not encode for proteins. This is the first time scientists have found mutations in this area of the cancer genome. (Previously, cancer genes have only been discovered in the protein-encoding region of the genome.) However, researchers found that these might be the most common mutations in melanoma cells.

 The researchers discovered the mutations by sifting through whole-genome sequences of cells taken from malignant melanoma tumors. These mutations are present in other malignancies, especially hepatocellular and bladder cancers. The researchers noted that this result prompted them to look at cancer tumors’ entire genomes.

 Doing so in the melanoma tumors led the researchers to a region that regulates and controls telomerase reverse transcriptase (TERT), which signals to increase telomerase production. Telomerase, in turn, prolongs cell life by allowing indefinite cell division and circumventing apoptosis (programmed cell death). In melanoma, the researchers were also able to show that TERT mutations share genetic hallmarks with other ultraviolet light–induced mutations.

 TERT is expressed in 90% of cancers. The mechanism in other cancers may be the same as or similar to that identified in melanoma. TERT has been an elusive target for drug development, but this finding may renew interest and help researchers think outside the box and find new approaches.