TY - JOUR
T1 - Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma
AU - Gartner, Jared J.
AU - Parker, Stephen C.J.
AU - Prickett, Todd D.
AU - Dutton-Regester, Ken
AU - Stitzel, Michael L.
AU - Lin, Jimmy C.
AU - Davis, Sean
AU - Simhadri, Vijaya L.
AU - Jha, Sujata
AU - Katagiri, Nobuko
AU - Gotea, Valer
AU - Teer, Jamie K.
AU - Wei, Xiaomu
AU - Morken, Mario A.
AU - Bhanot, Umesh K.
AU - Chen, Guo
AU - Elnitski, Laura L.
AU - Davies, Michael A.
AU - Gershenwald, Jeffrey E.
AU - Carter, Hannah
AU - Karchin, Rachel
AU - Robinson, William
AU - Robinson, Steven
AU - Rosenberg, Steven A.
AU - Collins, Francis S.
AU - Parmigiani, Giovanni
AU - Komar, Anton A.
AU - Kimchi-Sarfaty, Chava
AU - Hayward, Nicholas K.
AU - Margulies, Elliott H.
AU - Samuels, Yardena
PY - 2013/8/13
Y1 - 2013/8/13
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.1304227110
DO - 10.1073/pnas.1304227110
M3 - Article
C2 - 23901115
AN - SCOPUS:84882330643
SN - 0027-8424
VL - 110
SP - 13481
EP - 13486
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 33
ER -