title: The functional relevance of somatic synonymous mutations in melanoma and other cancers.
abstract: Recent technological advances in sequencing have flooded the field of cancer research with knowledge about somatic mutations for many different cancer types. Most cancer genomics studies focus on mutations that alter the amino acid sequence, ignoring the potential impact of synonymous mutations. However, accumulating experimental evidence has demonstrated clear consequences for gene function, leading to a widespread recognition of the functional role of synonymous mutations and their causal connection to various diseases. Here, we review the evidence supporting the direct impact of synonymous mutations on gene function via gene splicing; mRNA stability, folding, and translation; protein folding; and miRNA-based regulation of expression. These results highlight the functional contribution of synonymous mutations to oncogenesis and the need to further investigate their detection and prioritization for experimental assessment.
authors: Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
authors: Valer
authors: V
authors: Gotea
authors: Surgery Branch, National Cancer Institute, NIH, Bethesda, MD, USA.
authors: Jared J
authors: JJ
authors: Gartner
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors: Nouar
authors: N
authors: Qutob
authors: Translational and Functional Genomics Branch, National Human Genome Research Institute, NIH, Bethesda, MD, USA.
authors: Laura
authors: L
authors: Elnitski
authors: Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
authors: Yardena
authors: Y
authors: Samuels
mesh_terms: D019295:Computational Biology; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*
keywords: cancer; gene splicing; melanoma; miRNA regulation; protein folding; protein translation; secondary structure; synonymous mutations