TY - JOUR
T1 - A highly recurrent RPS27 5'UTR mutation in melanoma
AU - Dutton-Regester, Ken
AU - Gartner, Jared J.
AU - Emmanuel, Rafi
AU - Qutob, Nouar
AU - Davies, Michael A.
AU - Gershenwald, Jeffrey E.
AU - Robinson, William
AU - Robinson, Steven
AU - Steven, A. Rosenberg
AU - Scolyer, Richard A.
AU - Mann, Graham J.
AU - Thompson, John F.
AU - Hayward, Nicholas K.
AU - Samuels, Yardena
N1 - National Human Genome Research Institute; National Institutes of Health, USA; University of Texas MD Anderson Cancer Center Melanoma SPORE [P50CA093459]; National Health and Medical Research Council (NHMRC) of Australia; Israel Science Foundation [1604/13, 877/13]; ERC [StG-335377]; Dukler Fund for Cancer Research; Comisaroff Family Trust; NHRMC; Gideon Hamburger, IsraelThis work was supported by the Intramural Research Programs of the National Human Genome Research Institute, National Institutes of Health, USA, The University of Texas MD Anderson Cancer Center Melanoma SPORE (P50CA093459) and the National Health and Medical Research Council (NHMRC) of Australia. YS is supported by the Israel Science Foundation grant numbers 1604/13 and 877/13, the ERC (StG-335377), Dukler Fund for Cancer Research, Comisaroff Family Trust and Gideon Hamburger, Israel. NKH and KD-R are supported by fellowships from the NHRMC. The authors gratefully acknowledge the assistance of Gulietta Pupo, Varsha Tembe, Candace Carter and other colleagues from Melanoma Institute Australia, Royal Prince Alfred Hospital and Westmead Millennium Institute, Sydney, Australia.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84902105555&partnerID=8YFLogxK
U2 - https://doi.org/10.18632/oncotarget.2048
DO - https://doi.org/10.18632/oncotarget.2048
M3 - مقالة
SN - 1949-2553
VL - 5
SP - 2912
EP - 2917
JO - Oncotarget
JF - Oncotarget
IS - 10
ER -