Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Franz X Schaub, Varsha Dhankani, Ashton C Berger, Mihir Trivedi, Anne B Richardson, Reid Shaw, Wei Zhao, Xiaoyang Zhang, Andrea Ventura, Yuexin Liu, Donald E Ayer, Peter J Hurlin, Andrew D Cherniack, Robert N Eisenman, Brady Bernard, Carla Grandori
CELL SYSTEMS | CELL PRESS | Published : 2018
Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesti..View full abstract
Awarded by NIH
Awarded by NATIONAL CANCER INSTITUTE
Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE
The MYC team would like to acknowledge Dr. Theo Knijnenburg for guidance and discussions regarding the statistical analysis and interpretation conducted as part of this research. We would also like to thank Dr. Bruno Amati, Dr. Christopher Kemp, and Dr. Goldie Lui for helpful input on the manuscript. This work was supported in part with grants from NIH (4U01CA176303-04 to C.G., U24CA143867 to A.C.B. and A.D.C., RO1CA57138 to R.N.E., and 5R01CA149707 to A.V.) and research funding from SEngine Precision Medicine and Cure First to C.G., F.X.S., V.D., and R.S.P. J.H. is supported by grants from Shriners Hospitals for Children and Leukemia and Lymphoma Society.The TCGA Research network was funded by the following grants: U54 HG003273 to R.A. Gibbs, U54 HG003067 to S. Gabriel and E.S. Lander, U54 HG003079 to R.K. Wilson, U24 CA143799 to T.P. Speed and P.T. Spellman, U24 CA143835 to I. Shmulevich, U24 CA143840 to M. Ladanyi and C. Sander, U24 CA143843 to R.A. Gibbs and D.A. Wheeler, U24 CA143845 to L. Chin and G. Getz, U24 CA143848 to D.N. Hayes and C.M. Perou, U24 CA143858 to J. Stuart, C. Benz, and D.H. Haussler, U24 CA143866 to M.A. Marra, U24 CA143867 to S. Gabriel and M. L. Meyerson, U24 CA143882 to S.B. Baylin and P.W. Laird, U24 CA143883 to G.B. Mills, J.N. Weinstein, R. Akbani, and W.K.A. Yung, U24 CA144025 to R.S. Kucherlapati, and P30 CA016672 to G.B. Mills.