title: A highly recurrent RPS27 5'UTR mutation in melanoma.
abstract: The incidence of melanoma continues to rise globally and is increasing at a rate greater than any other cancer. To systematically search for new genes involved in melanomagenesis, we collated exome sequencing data from independent melanoma cohort datasets, including those in the public domain. We identified recurrent mutations that may drive melanoma growth, survival or metastasis, and which may hold promise for the design of novel therapies to treat melanoma. These included a frequent recurrent (i.e. hotspot) mutation in the 5' untranslated region of RPS27 in ~10% of samples. We show that the mutation expands the 5'TOP element, a motif known to regulate the expression of most of the ribosomal protein family, to which RPS27 belongs, and thus might sensitize the mutated transcript to growth-mediated regulation. This finding highlights not only the important role of non-protein coding genetic aberrations in cancer development but also their potential as novel therapeutic targets.
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
authors.forename: Ken
authors.initials: K
authors.lastname: Dutton-Regester
authors.affiliation: National Cancer Institute, NIH, MD, USA.
authors.forename: Jared J
authors.initials: JJ
authors.lastname: Gartner
authors.forename: Rafi
authors.initials: R
authors.lastname: Emmanuel
authors.forename: Nouar
authors.initials: N
authors.lastname: Qutob
authors.forename: Michael A
authors.initials: MA
authors.lastname: Davies
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.forename: William
authors.initials: W
authors.lastname: Robinson
authors.forename: Steven
authors.initials: S
authors.lastname: Robinson
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Mann
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Hayward
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yardena
authors.initials: Y
authors.lastname: Samuels
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D008667:Metalloproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D008667:Metalloproteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C083686:RPS27 protein, human; D012269:Ribosomal Proteins