title: RASopathy Gene Mutations in Melanoma.
abstract: Next-generation sequencing of melanomas has unraveled critical driver genes and genomic abnormalities, mostly defined as occurring at high frequency. In addition, less abundant mutations are present that link melanoma to a set of disorders, commonly called RASopathies. These disorders, which include neurofibromatosis and Noonan and Legius syndromes, harbor germline mutations in various RAS/mitogen-activated protein kinase signaling pathway genes. We highlight shared amino acid substitutions between this set of RASopathy mutations and those observed in large-scale melanoma sequencing data, uncovering a significant overlap. We review the evidence that these mutations activate the RAS/mitogen-activated protein kinase pathway in melanoma and are involved in melanomagenesis. Furthermore, we discuss the observations that two or more RASopathy mutations often co-occur in melanoma and may act synergistically on activating the pathway.
authors.affiliation: Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut, USA. Electronic address: ruth.halaban@yale.edu.
authors.forename: Ruth
authors.initials: R
authors.lastname: Halaban
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA; Program in Computational Biology and Bioinformatics, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Krauthammer
mesh_terms: D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D018095:Germ-Line Mutation; D006801:Humans; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics* / Q000503:physiopathology; D018631:ras Proteins / Q000235:genetics*
chemical_list: D018631:ras Proteins