Abstract
Melanoma has one of the highest somatic mutational burdens among solid malignancies. Although the rapid progress in genomic research has contributed immensely to our understanding of the pathogenesis of melanoma, the clinical significance of the vast array of genomic alterations discovered by next-generation sequencing is far from being fully characterized. Most mutations prevalent in melanoma are simply neutral "passengers," which accompany functionally significant "drivers" under transforming conditions. The delineation of driver mutations from passenger mutations is critical to the development of targeted therapies. Novel advances in genomic data analysis have aided in distinguishing true driver mutations involved in tumor progression. Here, the authors review the current literature on important somatic driver mutations in melanoma, along with the implications for treatment. Cancer 2017;123:2104-17. © 2017 American Cancer Society.
Keywords:
driver mutations; genetics; immune therapy; melanoma; targeted therapy.
© 2017 American Cancer Society.
MeSH terms
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Cyclin D1 / genetics
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GTP Phosphohydrolases / genetics
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GTP-Binding Protein alpha Subunits / genetics
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GTP-Binding Protein alpha Subunits, Gq-G11 / genetics
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Guanine Nucleotide Exchange Factors / genetics
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High-Throughput Nucleotide Sequencing
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Humans
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Melanoma / genetics*
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Membrane Proteins / genetics
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Metalloproteins / genetics
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Microphthalmia-Associated Transcription Factor / genetics
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Mutation*
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Neurofibromin 1 / genetics
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Nuclear Proteins / genetics
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PTEN Phosphohydrolase / genetics
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Proto-Oncogene Proteins B-raf / genetics
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Proto-Oncogene Proteins c-kit / genetics
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RNA-Binding Proteins / genetics
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Ribosomal Proteins / genetics
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Sequence Analysis, DNA
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Skin Neoplasms / genetics*
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Telomerase / genetics
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Tumor Suppressor Protein p53 / genetics
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Uveal Neoplasms / genetics*
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rac1 GTP-Binding Protein / genetics
Substances
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GNA11 protein, human
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GNAQ protein, human
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GTP-Binding Protein alpha Subunits
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Guanine Nucleotide Exchange Factors
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Membrane Proteins
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Metalloproteins
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Microphthalmia-Associated Transcription Factor
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Neurofibromin 1
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Nuclear Proteins
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PREX2 protein, human
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RAC1 protein, human
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RNA-Binding Proteins
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RPS27 protein, human
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Ribosomal Proteins
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Tumor Suppressor Protein p53
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Cyclin D1
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Proto-Oncogene Proteins c-kit
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Proto-Oncogene Proteins B-raf
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TERT protein, human
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Telomerase
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PTEN Phosphohydrolase
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GTP Phosphohydrolases
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NRAS protein, human
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GTP-Binding Protein alpha Subunits, Gq-G11
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rac1 GTP-Binding Protein