Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types
Publication date
2018-04-03
Authors
Ge, Zhongqi
Leighton, Jake S.
Wang, Yumeng
Peng, Xinxin
Chen, Zhongyuan
Chen, Hu
Sun, Yutong
Yao, Fan
Li, Jun
Zhang, Huiwen
Editors
Advisors
Supervisors
Document Type
Article
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License
cc_by_nc_nd
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 multiomic data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the upregulation of cell-cycle and DNA repair pathways, characterized by mutated TP53, MYC/TERT amplification, and APC/PTEN deletion. Our analysis highlights the importance of the ubiquitin pathway in cancer development and lays a foundation for developing relevant therapeutic strategies.
Keywords
biomarker, cancer prognosis, FBXW7, pan-cancer analysis, The Cancer Genome Atlas, therapeutic targets, tumor subtype, ubiquitin pathway, Humans, Gene Expression Regulation, Neoplastic, Genomics/methods, Ubiquitination, Oncogene Proteins/genetics, Metabolic Networks and Pathways, Neoplasms/classification, Cell Line, Tumor, Genome, Human, General Biochemistry,Genetics and Molecular Biology, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Journal Article, Research Support, N.I.H., Extramural
Citation
Ge, Z, Leighton, J S, Wang, Y, Peng, X, Chen, Z, Chen, H, Sun, Y, Yao, F, Li, J, Zhang, H, Liu, J, Shriver, C D, Hu, H, Caesar-Johnson, S J, Demchok, J A, Felau, I, Kasapi, M, Ferguson, M L, Hutter, C M, Sofia, H J, Tarnuzzer, R, Wang, Z, Yang, L, Zenklusen, J C, Zhang, J, Chudamani, S, Liu, J, Lolla, L, Naresh, R, Pihl, T, Sun, Q, Wan, Y, Wu, Y, Cho, J, DeFreitas, T, Frazer, S, Gehlenborg, N, Getz, G, Heiman, D I, Kim, J, Lawrence, M S, Lin, P, Meier, S, Noble, M S, Saksena, G, Voet, D, Zhang, H, Bernard, B, Chambwe, N, de Krijger, R & The Cancer Genome Atlas Research Network 2018, 'Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types', Cell Reports, vol. 23, no. 1, pp. 213-226.e3. https://doi.org/10.1016/j.celrep.2018.03.047