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

• DOI: 10.1073/pnas.1304227110
• Publication Date: 2013-07-31T07:25:22Z
• 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. Gershe...; 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
• Keywords: Cancer genome sequencing

Synonymous mutations, which do not alter the protein sequence, have been shown to affect function [Sauna ZE, Kimchi-Sarfaty C (2011) Nat Rev Genet 12(10):683–691]. However, synonymous mutations are rarely investigated in cancer genomics field. We used whole-genome and -exome sequencing identify somatic 29 melanoma samples. Validation of one mutation BCL2L12 285 samples identified 12 cases that harbored recurrent F17F mutation. This led increased mRNA levels because differential targeting WT mutant by hsa-miR-671–5p. Protein made from transcript bound p53, inhibited UV-induced apoptosis more efficiently than , reduced endogenous p53 target gene transcription. report shows selection a cancer. Our data indicate silent alterations role play human cancer, emphasizing importance their investigation future genome studies.