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Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13481-6. doi: 10.1073/pnas.1304227110. Epub 2013 Jul 30.

Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma.

Author information

1
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Erratum in

  • Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):563.

Abstract

Synonymous mutations, which do not alter the protein sequence, have been shown to affect protein function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683-691]. However, synonymous mutations are rarely investigated in the cancer genomics field. We used whole-genome and -exome sequencing to identify somatic mutations in 29 melanoma samples. Validation of one synonymous somatic mutation in BCL2L12 in 285 samples identified 12 cases that harbored the recurrent F17F mutation. This mutation led to increased BCL2L12 mRNA and protein levels because of differential targeting of WT and mutant BCL2L12 by hsa-miR-671-5p. Protein made from mutant BCL2L12 transcript bound p53, inhibited UV-induced apoptosis more efficiently than WT BCL2L12, and reduced endogenous p53 target gene transcription. This report shows selection of a recurrent somatic synonymous mutation in cancer. Our data indicate that silent alterations have a role to play in human cancer, emphasizing the importance of their investigation in future cancer genome studies.

PMID:
23901115
PMCID:
PMC3746936
DOI:
10.1073/pnas.1304227110
[Indexed for MEDLINE]
Free PMC Article

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