| 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. |
| Keywords: |
controlled study; protein expression; unclassified drug; oncoprotein; gene mutation; gene sequence; human cell; mutation; polymorphism, single nucleotide; ultraviolet radiation; melanoma; apoptosis; rna, small interfering; gene frequency; genetic transcription; protein p53; genetic vectors; gene expression regulation; blotting, western; molecular sequence data; messenger rna; nucleotide sequence; immunoprecipitation; lentivirus; rna translation; tumor suppressor protein p53; base sequence; dna primers; micrornas; proto-oncogene proteins c-bcl-2; genome, human; sequence analysis, dna; hek293 cells; muscle proteins; real-time polymerase chain reaction; exome; microrna 671 5p; protein bcl 12
|
| Notes: |
---
- "Export Date: 1 October 2013"
- "CODEN: PNASA"
- "Molecular Sequence Numbers: GENBANK: NM_001372, NM_001876, NM_002711, NM_006229, NM_007254, NM_015687, NM_016426, NM_021110, NM_052938, NM_133378, NM_138639, NM_174981"
- "Source: Scopus"
|
