Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

The Cancer Genome Atlas Research Network

    Research output: Contribution to journalArticlepeer-review

    77 Citations (Scopus)

    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. Ge et al. analyze a cohort of 9,125 TCGA samples across 33 cancer types to provide a comprehensive characterization of the ubiquitin pathway. They detect somatic driver candidates in the ubiquitin pathway and identify a cluster of patients with poor survival, highlighting the importance of this pathway in cancer development.

    Original languageEnglish
    Pages (from-to)213-226.e3
    JournalCell Reports
    Volume23
    Issue number1
    DOIs
    Publication statusPublished - 3 Apr 2018

    Keywords

    • FBXW7
    • The Cancer Genome Atlas
    • biomarker
    • cancer prognosis
    • pan-cancer analysis
    • therapeutic targets
    • tumor subtype
    • ubiquitin pathway

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