Synonymous mutations frequently act as driver mutations in human cancers - PubMed (original) (raw)
. 2014 Mar 13;156(6):1324-1335.
doi: 10.1016/j.cell.2014.01.051.
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- PMID: 24630730
- DOI: 10.1016/j.cell.2014.01.051
Free article
Synonymous mutations frequently act as driver mutations in human cancers
Fran Supek et al. Cell. 2014.
Free article
Abstract
Synonymous mutations change the sequence of a gene without directly altering the sequence of the encoded protein. Here, we present evidence that these "silent" mutations frequently contribute to human cancer. Selection on synonymous mutations in oncogenes is cancer-type specific, and although the functional consequences of cancer-associated synonymous mutations may be diverse, they recurrently alter exonic motifs that regulate splicing and are associated with changes in oncogene splicing in tumors. The p53 tumor suppressor (TP53) also has recurrent synonymous mutations, but, in contrast to those in oncogenes, these are adjacent to splice sites and inactivate them. We estimate that between one in two and one in five silent mutations in oncogenes have been selected, equating to ~6%- 8% of all selected single-nucleotide changes in these genes. In addition, our analyses suggest that dosage-sensitive oncogenes have selected mutations in their 3' UTRs.
Copyright © 2014 Elsevier Inc. All rights reserved.
Comment in
- Silent mutations make some noise.
Zheng S, Kim H, Verhaak RGW. Zheng S, et al. Cell. 2014 Mar 13;156(6):1129-1131. doi: 10.1016/j.cell.2014.02.037. Cell. 2014. PMID: 24630716
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