Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Z Ge; JS Leighton; Y Wang; X Peng; Z Chen; H Chen; Y Sun; F Yao; J Li; H Zhang; J Liu; CD Shriver; H Hu; SJ Caesar-Johnson; JA Demchok; I Felau; M Kasapi; ML Ferguson; CM Hutter; HJ Sofia; R Tarnuzzer; Z Wang; L Yang; JC Zenklusen; J Zhang; S Chudamani; J Liu; L Lolla; R Naresh; T Pihl; Q Sun; Y Wan; Y Wu; J Cho; T DeFreitas; S Frazer; N Gehlenborg; G Getz; DI Heiman; J Kim; MS Lawrence; P Lin; S Meier; MS Noble; G Saksena; D Voet; H Zhang; B Bernard; N Chambwe; V Dhankani; T Knijnenburg; R Kramer; K Leinonen; Y Liu; M Miller; S Reynolds; I Shmulevich; V Thorsson; W Zhang; R Akbani; BM Broom; AM Hegde; Z Ju; RS Kanchi; A Korkut; H Liang; S Ling; W Liu; Y Lu; GB Mills; KS Ng; A Rao; M Ryan; J Wang; JN Weinstein; J Zhang; A Abeshouse; J Armenia; D Chakravarty; WK Chatila; I de Bruijn; J Gao; BE Gross; ZJ Heins; R Kundra; K La; M Ladanyi; A Luna; MG Nissan; A Ochoa; SM Phillips; E Reznik; F Sanchez-Vega; C Sander; N Schultz; R Sheridan; SO Sumer; Y Sun; BS Taylor; J Wang

Journal article

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Z Ge, JS Leighton, Y Wang, X Peng, Z Chen, H Chen, Y Sun, F Yao, J Li, H Zhang, J Liu, CD Shriver, H Hu, SJ Caesar-Johnson, JA Demchok, I Felau, M Kasapi, ML Ferguson, CM Hutter, HJ Sofia Show all

Cell Reports | CELL PRESS | Published : 2018

DOI: 10.1016/j.celrep.2018.03.047

Open access

Abstract

Protein ubiquitination is a dynamic and reversible process of adding single ubiquitin molecules or various ubiquitin chains to target proteins. Here, using multidimensional omic data of 9,125 tumor samples across 33 cancer types from The Cancer Genome Atlas, we perform comprehensive molecular characterization of 929 ubiquitin-related genes and 95 deubiquitinase genes. Among them, we systematically identify top somatic driver candidates, including mutated FBXW7 with cancer-type-specific patterns and amplified MDM2 showing a mutually exclusive pattern with BRAF mutations. Ubiquitin pathway genes tend to be upregulated in cancer mediated by diverse mechanisms. By integrating pan-cancer multiomi..

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University of Melbourne Researchers

Christopher Hovens Author

Michael Lawrence Author

Alex Boussioutas Author

Niall Corcoran Author

Grants

Awarded by University of Texas System

Funding Acknowledgements

This study was supported in part by the NIH (R01CA175486 and U24CA209851 to H.L., R01CA166051 and R01CA181029 to L. M., U54HG003273, U54HG003067, U54HG003079, U24CA143799, U24CA143835, U24CA143840, U24CA143843, U24CA143845, U24CA143848, U24CA143858, U24CA143866, U24CA143867, U24CA143882, U24CA143883, U24CA144025, and P30CA016672), the Cancer Prevention and Research Institute of Texas (RP140462 to H.L. and RP150319 to L.M.), a Stand Up To Cancer Innovative Research Grant (to L. M.), a University of Texas System STARS award (to H.L.), and the US Department of Defense through the Henry M. Jackson Foundation for the Advancement of Military Medicine (W81XWH-12-2-0050, HU0001-16-2-0004). We thank the MD Anderson high-performance computing core facility for computing and LeeAnn Chastain for editorial assistance. The views expressed in this article are those of the authors and do not reflect the official policy of the U.S. Army, Navy, Air Force, Department of Defense, or government.