Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ge, Z; Leighton, JS; Wang, Y; Peng, X; Chen, Z; Chen, H; Sun, Y; Yao, F; Li, J; Zhang, H; Liu, J; Shriver, CD; Hu, H; Cancer Genome Atlas Research Network, ; Piwnica-Worms, H; Ma, L; Liang, H

Published Date

  • April 3, 2018

Published In

Volume / Issue

  • 23 / 1

Start / End Page

  • 213 - 226.e3

PubMed ID

  • 29617661

Pubmed Central ID

  • PMC5916807

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2018.03.047


  • eng

Conference Location

  • United States