Title |
Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma
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Published in |
Proceedings of the National Academy of Sciences of the United States of America, July 2013
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DOI | 10.1073/pnas.1304227110 |
Pubmed ID | |
Authors |
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 Carter, Rachel 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, Jesse Becker, Betty Benjamin, Robert Blakesley, Gerry Bouffard, Shelise Brooks, Holly Coleman, Mila Dekhtyar, Michael Gregory, Xiaobin Guan, Jyoti Gupta, Joel Han, April Hargrove, Shi-ling Ho, Taccara Johnson, Richelle Legaspi, Sean Lovett, Quino Maduro, Cathy Masiello, Baishali Maskeri, Jenny McDowell, Casandra Montemayor, James Mullikin, Morgan Park, Nancy Riebow, Karen Schandler, Brian Schmidt, Christina Sison, Mal Stantripop, James Thomas, Pam Thomas, Meg Vemulapalli, Alice Young |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 29% |
Australia | 1 | 14% |
Italy | 1 | 14% |
United Kingdom | 1 | 14% |
Germany | 1 | 14% |
Unknown | 1 | 14% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 4 | 57% |
Members of the public | 3 | 43% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 4 | 2% |
Netherlands | 2 | <1% |
United Kingdom | 2 | <1% |
Korea, Republic of | 1 | <1% |
Australia | 1 | <1% |
Brazil | 1 | <1% |
Sweden | 1 | <1% |
Germany | 1 | <1% |
Denmark | 1 | <1% |
Other | 3 | 1% |
Unknown | 186 | 92% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 47 | 23% |
Researcher | 39 | 19% |
Student > Master | 23 | 11% |
Professor | 14 | 7% |
Student > Bachelor | 11 | 5% |
Other | 44 | 22% |
Unknown | 25 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 87 | 43% |
Biochemistry, Genetics and Molecular Biology | 47 | 23% |
Medicine and Dentistry | 22 | 11% |
Engineering | 3 | 1% |
Immunology and Microbiology | 2 | <1% |
Other | 14 | 7% |
Unknown | 28 | 14% |