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

Jared J. Gartner, Stephen C.J. Parker, Todd D. Prickett, Ken Dutton-Regester, Michael L. Stitzel, Jimmy C. Lin, Sean Davis, Vijaya L. Simhadri, Sujata Jha, Nobuko Katagiri, Valer Gotea, Jamie K. Teer, Xiaomu Wei, Mario A. Morken, Umesh K. Bhanot, Guo Chen, Laura L. Elnitski, Michael A. Davies, Jeffrey E. Gershenwald, Hannah CarterRachel Karchin, William Robinson, Steven Robinson, Steven A. Rosenberg, Francis S. Collins, Giovanni Parmigiani, Anton A. Komar, Chava Kimchi-Sarfaty, Nicholas K. Hayward, Elliott H. Margulies, Yardena Samuels

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)13481-13486
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number33
StatePublished - Aug 13 2013
Externally publishedYes

ASJC Scopus subject areas

  • General


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