Driver Mutations found in Melanoma

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(ChemotherapyAdvisor) – Several mutations found in melanoma act to drive tumorigenesis, according to an international team of researchers. This conclusion is based on a study entitled “A Landscape of Driver Mutations in Melanoma,” which was published in Cell on July 20.

The investigators based the design of this study on the following lines of evidence. First, there have been numerous recent insights into melanoma genetics. Second, systematic surveys for driver mutations are challenged by an abundance of passenger mutations caused by carcinogenic UV light exposure, they wrote. To identify driver mutations in melanoma, the investigators developed a framework to address this challenge on a per gene basis.

Using their framework, the investigators discovered the following genes using large-scale melanoma exome data: PPP6C, RAC1, SNX31, TACC1, STK19, and ARID2. Three of these genes—RAC1, PPP6C, and STK19—“harbored recurrent and potentially targetable mutations,” the investigators wrote. Further analyses revealed BRAF- and NRAS-driven melanoma as well as melanoma driven without known NRAS/BRAF mutations. “The spectrum of driver mutations provided unequivocal genomic evidence for a direct mutagenic role of UV light in melanoma pathogenesis,” the investigators wrote.

The following conclusions were drawn based on the reported data. First, PPP6C, RAC1, SNX31, TACC1, STK19, and ARID2 are significantly mutated melanoma genes. Second, signature spectrum of UV mutagenesis accounts for 46% of driver mutations found.

Abstract

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