A highly recurrent RPS27 5 ' UTR mutation in melanoma

作者：Dutton Regester Ken; Gartner Jared J; Emmanuel Rafi; Qutob Nouar; Davies Michael A; Gershenwald Jeffrey E; Robinson William; Robinson Steven; Steven A Rosenberg; Scolyer Richard A; Mann Graham J; Thompson John F; Hayward Nicholas K; Samuels Yardena^*

来源：Oncotarget, 2014, 5(10): 2912-2917.

DOI：10.18632/oncotarget.2048

• Melanoma
• somatic mutation
• RPS27
• exome sequencing
• 5 ' untranslated region

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 similar to 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.

• 出版日期2014-5