Journal article

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Zhongqi Ge, Jake S Leighton, Yumeng Wang, Xinxin Peng, Zhongyuan Chen, Hu Chen, Yutong Sun, Fan Yao, Jun Li, Huiwen Zhang, Jianfang Liu, Craig D Shriver, Hai Hu, Helen Piwnica-Worms, Li Ma, Han Liang

CELL REPORTS | CELL PRESS | Published : 2018

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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Grants

Awarded by NIH


Awarded by Cancer Prevention and Research Institute of Texas


Awarded by US Department of Defense through the Henry M. Jackson Foundation for the Advancement of Military Medicine


Awarded by NATIONAL CANCER INSTITUTE


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.