Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Cell Reports. Volume 23 Issue 1: p213–226.e3, 3 April 2018 10.1016/j.celrep.2018.03.047

Protein ubiquitination is a dynamic and reversible process by 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 multi-omics data, we identify a group of tumor samples that exhibit worse prognosis. These samples are consistently associated with the 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.

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Supplemental Data

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• MAF Files
  • TCGA somatic mutation data - mc3.v0.2.8.PUBLIC.maf.gz
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  • TCGA gene expression data - EBPlusPlusAdjustPANCAN_IlluminaHiSeq_RNASeqV2.geneExp.tsv
  • TCGA somatic copy number thresholded data - all_thresholded.by_genes_whitelisted.tsv
  • TCGA somatic copy number alteration SNP6 segmentation file - broad.mit.edu_PANCAN_Genome_Wide_SNP_6_whitelisted.seg
  • TCGA DNA methylation data - jhu-usc.edu_PANCAN_HumanMethylation450.betaValue_whitelisted.tsv
  • TCGA miRNA expression data - bcgsc.ca_PANCAN_IlluminaHiSeq_miRNASeq.miRNAExp_whitelisted.tsv
  • TCGA miRNA expression data - bcgsc.ca_PANCAN_IlluminaGA_miRNASeq.miRNAExp_whitelisted.tsv
  • TCGA RPPA data - mdanderson.org_PANCAN_MDA_RPPA_Core.RPPA_whitelisted.tsv

Additional Resources

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• cBioPortal for Cancer Genomics (link is external) Memorial Sloan-Kettering Cancer Center
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• TCPA (link is external)

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