CELL BIOLOGYCorrection for Phosphoproteomic characterization of DNA dam-age response in melanoma cells following MEK/PI3K dual in-hibition, by Donald S. Kirkpatrick, Daisy J. Bustos, Taner Dogan,Jocelyn Chan, Lilian Phu, Amy Young, Lori S. Friedman, MarciaBelvin, Qinghua Song, Corey E. Bakalarski, and Klaus P. Hoeflich,
which appeared in issue 48, November 26, 2013, of Proc NatlAcad Sci USA (110:1942619431; first published November 11,2013; 10.1073/pnas.1309473110).The authors note that Figure 1 appeared incorrectly. The cor-
rected figure and its legend appear below.
pRSK pAKTpERK pS6
- + - + - + - + - + - + - + - + - + - + - + - +
- + - + - + - + - + - + - + - + - + - + - + - +
- +A2058: DMSO (-) vs MEKi/PI3Ki combo (+)
888MEL: DMSO (-) vs MEKi/PI3Ki combo (+)
EC50 0 0 0.25 0.25 .25.5 .5 .51 1 1 222 4 4 4
MEKi PI3Ki MEKi + Pi3Ki
B - + - +MEKi - - + +PI3Ki
- + - +
- - + +
Fig. 1 Dual inhibition of MEK and PI3K induces phosphorylation of DDR substrates. (A) A2058 or 888MEL melanoma cells were treated for 6 h with DMSO orGDC-0973+GDC-0941 (MEKi/PI3Ki combo; 4 EC50) and were subjected to KinomeView Profiling. A2058 and 888MEL cells were treated with 10 M GDC-0973 +10 M GDC-0941 or 0.2 M GDC-0973 + 10 M GDC-0941, respectively. Blots were probed using an antibody mixture recognizing pRSK, pAKT, pERK, and pS6 orphosphomotif antibodies (e.g., DDR substrates with the [s/t]Q motif and AKT substrates with the RXX[s/t] and RXRXX[s/t] motifs). (B) A2058 lysates probed withthe [s/t]Q and RXX[s/t] antibodies after treatment with DMSO, 10 MGDC-0973 (MEKi), 10 MGDC-0941 (PI3Ki), or the combination. (C) Dose response of A2058cells to increasing concentrations of MEKi and PI3Ki alone or in combination. Blots were performed against DDR (p53 pSer15, histone 2AX pSer139), cell survival/cell death (AKT pThr308, cleaved PARP), and cell signaling (ERK1/2 pThr202/Tyr204) markers and controls. Actin and GAPDH served as loading controls.
562563 | PNAS | January 7, 2014 | vol. 111 | no. 1 www.pnas.org
ENVIRONMENTAL SCIENCESCorrection for Genome of an arbuscular mycorrhizal fungusprovides insight into the oldest plant symbiosis, by EmilieTisserant, Mathilde Malbreil, Alan Kuo, Annegret Kohler,Aikaterini Symeonidi, Raffaella Balestrini, Philippe Charron,Nina Duensing, Nicolas Frei dit Frey, Vivienne Gianinazzi-Pearson,Luz B. Gilbert, Yoshihiro Handa, Joshua R. Herr, MohamedHijri, Raman Koul, Masayoshi Kawaguchi, Franziska Krajinski,Peter J. Lammers, Frederic G. Masclaux, Claude Murat,Emmanuelle Morin, Steve Ndikumana, Marco Pagni, DenisPetitpierre, Natalia Requena, Pawel Rosikiewicz, Rohan Riley,Katsuharu Saito, Hlne San Clemente, Harris Shapiro, Diederikvan Tuinen, Guillaume Bcard, Paola Bonfante, Uta Paszkowski,Yair Y. Shachar-Hill, Gerald A. Tuskan, Peter W. Young, Ian R.Sanders, Bernard Henrissat, Stefan A. Rensing, Igor V. Grigoriev,Nicolas Corradi, Christophe Roux, and Francis Martin, whichappeared in issue 50, December 10, 2013, of Proc Natl Acad SciUSA (110:2011720122; first published November 25, 2013;10.1073/pnas.1313452110).The authors note that the author name Peter W. Young
should instead appear as J. Peter W. Young. The corrected au-thor line appears below. The online version has been corrected.
Emilie Tisserant, Mathilde Malbreil, Alan Kuo, AnnegretKohler, Aikaterini Symeonidi, Raffaella Balestrini,Philippe Charron, Nina Duensing, Nicolas Frei dit Frey,Vivienne Gianinazzi-Pearson, Luz B. Gilbert, YoshihiroHanda, Joshua R. Herr, Mohamed Hijri, Raman Koul,Masayoshi Kawaguchi, Franziska Krajinski, Peter J.Lammers, Frederic G. Masclaux, Claude Murat,Emmanuelle Morin, Steve Ndikumana, Marco Pagni,Denis Petitpierre, Natalia Requena, Pawel Rosikiewicz,Rohan Riley, Katsuharu Saito, Hlne San Clemente,Harris Shapiro, Diederik van Tuinen, Guillaume Bcard,Paola Bonfante, Uta Paszkowski, Yair Y. Shachar-Hill,Gerald A. Tuskan, J. Peter W. Young, Ian R. Sanders,Bernard Henrissat, Stefan A. Rensing, Igor V. Grigoriev,Nicolas Corradi, Christophe Roux, and Francis Martin
GENETICSCorrection for Whole-genome sequencing identifies a recurrentfunctional synonymous mutation in melanoma, by 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, NISCComparative Sequencing Program, 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, and Yardena Samuels, which appeared in issue 33,August 13, 2013, of Proc Natl Acad Sci USA (110:1348113486;first published July 30, 2013; 10.1073/pnas.1304227110).The authors note that the following statement should be
added to the Acknowledgments: Y.S. is supported by the IsraelScience Foundation (Grants 1604/13 and 877/13) and the Eu-ropean Research Council (Grant StG-335377).
MEDICAL SCIENCESCorrection for Integrin 1-focal adhesion kinase signalingdirects the proliferation of metastatic cancer cells dissemi-nated in the lungs, by Tsukasa Shibue and Robert A. Weinberg,which appeared in issue 25, June 23, 2009, of Proc Natl Acad SciUSA (106:1029010295; first published June 5, 2009; 10.1073/pnas.0904227106).The authors note that on page 10295, right column, 2nd full
paragraph, line 8 10 mg/kg xylene should instead appear as10 mg/kg xylazine.
PNAS | January 7, 2014 | vol. 111 | no. 1 | 563
Whole-genome sequencing identifies a recurrentfunctional synonymous mutation in melanomaJared J. Gartnera,1, Stephen C. J. Parkera,1, Todd D. Pricketta, Ken Dutton-Regesterb, Michael L. Stitzela, Jimmy C. Linc,Sean Davisd, Vijaya L. Simhadrie, Sujata Jhaf, Nobuko Katagirie, Valer Goteaa, Jamie K. Teera, Xiaomu Weia,Mario A. Morkena, Umesh K. Bhanotg, NISC Comparative Sequencing Programa,2, Guo Chenh, Laura L. Elnitskia,Michael A. Daviesh, Jeffrey E. Gershenwaldh, Hannah Carteri, Rachel Karchini, William Robinsonj, Steven Robinsonj,Steven A. Rosenbergd, Francis S. Collinsa, Giovanni Parmigianik,l, Anton A. Komarf, Chava Kimchi-Sarfatye,Nicholas K. Haywardb, Elliott H. Marguliesa,m, and Yardena Samuelsa,n,3
aNational Human Genome Research Institute and dNational Cancer Institute, National Institutes of Health, Bethesda, MD 20892; bDivision of Genetics andComputational Biology, Queensland Institute of Medical Research, Brisbane, QLD 4006, Australia; cDepartment of Pathology and Immunology, WashingtonUniversity School of Medicine, St. Louis, MO 63110; eLaboratory of Hemostasis, Division of Hematology, Center for Biologics Evaluation and Research,Food and Drug Administration, Bethesda, MD 20892; fCenter for Gene Regulation in Health and Disease and the Department of Biological, Geological, andEnvironmental Sciences, Cleveland State University, Cleveland, OH 44115; gDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York,NY 10065; hDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030; iDepartment of BiomedicalEngineering, Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218; jDivision of Medical Oncology, University of ColoradoSchool of Medicine, Aurora, CO 80045; kDepartment of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, MA 02115;lDepartment of Biostatistics, Harvard School of Public Health, Boston, MA 02115; mIllumina United Kingdom, Chesterford Research Park, Little Chesterford,Nr Saffron Walden, Essex CB10 1XL, United Kingdom; and nDepartment of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
Edited* by Bert Vogelstein, Johns Hopkins University, Baltimore, MD, and approved June 27, 2013 (received for review March 12, 2013)
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):683691]. However, synon-ymous mutations are rarely investigated in the cancer genomicsfield. We used whole-genome and -exome sequencing to identifysomatic mutations in 29 melanoma samples. Validation of onesynonymous somatic mutation in BCL2L12 in 285 samples identi-fied 12 cases that harbored the recurrent F17F mutation. This mu-tation led to increased BCL2L12 mRNA and protein levels becauseof differential targeting of WT and mutant BCL2L12 by hsa-miR-6715p. 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 reportshows selection of a recurrent somatic synonymous mutation incancer. Our data indicate that silent alterations have a role to playin human cancer, emphasizing the importance