Oncotarget

Priority Research Papers:

A highly recurrent RPS27 5’UTR mutation in melanoma

Ken Dutton-Regester, Jared J. Gartner, Rafi Emmanuel, Nouar Qutob, Michael A. Davies, Jeffrey E. Gershenwald, William Robinson, Steven Robinson, Steven A. Rosenberg, Richard A. Scolyer, Graham J. Mann, John F. Thompson, Nicholas K. Hayward and Yardena Samuels _

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Oncotarget. 2014; 5:2912-2917. https://doi.org/10.18632/oncotarget.2048

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Abstract

Ken Dutton-Regester1,*, Jared J. Gartner2,*, Rafi Emmanuel3, Nouar Qutob3, Michael A. Davies4, Jeffrey E. Gershenwald4, William Robinson5, Steven Robinson5, Steven A. Rosenberg2, Richard A. Scolyer6,7,8, Graham J. Mann6,9, John F. Thompson6,10,11, Nicholas K. Hayward1, Yardena Samuels3

1 QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

2 National Cancer Institute, NIH, MD, USA

3 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

4 The University of Texas MD Anderson Cancer Center, Houston, TX, USA

5 University of Colorado School of Medicine, Aurora, CO, USA

6 Melanoma Institute of Australia (formerly the Sydney Melanoma Unit), North Sydney,NSW, Australia

7 Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia

8 Discipline of Pathology, Sydney Medical School, The University of Sydney, NSW, Australia

9 University of Sydney at Westmead Millenium Institute, Westmead, NSW, Australia

10 Departments of Melanoma and Surgical Oncology, and Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

11 Discipline of Surgery, Sydney Medical School, The University of Sydney, Sydney, New South Wales, Australia

* These authors contributed equally to this work

Correspondence:

Yardena Samuels, email:

Nicholas K. Hayward, email:

Keywords: Melanoma, somatic mutation, RPS27, exome sequencing, 5’ untranslated region

Received: April 8, 2014 Accepted: May 30, 2014 Published: June 1, 2014

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.


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