The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data

Computational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Cancer Discovery (Impact Factor: 19.45). 05/2012; 2(5):401-4. DOI: 10.1158/2159-8290.CD-12-0095
Source: PubMed

ABSTRACT The cBio Cancer Genomics Portal ( is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications.

Download full-text


Available from: Erik Larsson Lekholm, Sep 29, 2015
60 Reads
    • "Increased rates of aerobic glycolysis and expression of glycolytic enzymes (e.g., hexokinase 2 [Hk2]) are common hallmarks of cancer cells (Hanahan and Weinberg, 2011), and this may lead to glucose-deprivation and T cell dysfunction in tumors as suggested by the data above. To investigate this hypothesis further, we analyzed the expression of effector T cell genes (e.g., Ifng and Cd40lg) and markers of glycolysis (e.g., Hk2) mRNA within the tumors of 384 melanoma patients (data obtained from The Cancer Genome Atlas [TCGA]) (Cerami et al., 2012; Gao et al., 2013). Interestingly, this showed that the amount of Cd40lg and Ifng mRNA inversely correlated with Hk2 mRNA (Figure S2A). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Activated T cells engage aerobic glycolysis and anabolic metabolism for growth, proliferation, and effector functions. We propose that a glucose-poor tumor microenvironment limits aerobic glycolysis in tumor-infiltrating T cells, which suppresses tumoricidal effector functions. We discovered a new role for the glycolytic metabolite phosphoenolpyruvate (PEP) in sustaining T cell receptor-mediated Ca(2+)-NFAT signaling and effector functions by repressing sarco/ER Ca(2+)-ATPase (SERCA) activity. Tumor-specific CD4 and CD8 T cells could be metabolically reprogrammed by increasing PEP production through overexpression of phosphoenolpyruvate carboxykinase 1 (PCK1), which bolstered effector functions. Moreover, PCK1-overexpressing T cells restricted tumor growth and prolonged the survival of melanoma-bearing mice. This study uncovers new metabolic checkpoints for T cell activity and demonstrates that metabolic reprogramming of tumor-reactive T cells can enhance anti-tumor T cell responses, illuminating new forms of immunotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell 08/2015; DOI:10.1016/j.cell.2015.08.012 · 32.24 Impact Factor
  • Source
    • "However, silencing PEAK1 in the CA1h cells completely blocked fibronectin-dependent, TGFβinduced ZEB1 expression (Figure 4B) and EMT [9]. Furthermore, a significant correlation (Pearson r = 0.76) exists between PEAK1 and ZEB1 expression in breast cancer patients (RNA-Seq data from 942 patients) (Figure 4C) [22] [23]. Finally, human breast cancer samples stained for PEAK1 and ZEB1 showed similar tissue and cellular localization (from the Human Protein Atlas) (Figure 4D) [24]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Transforming Growth Factor beta (TGFβ) is the archetypal member of the TGFβ superfamily of ligands and has pleiotropic functions during normal development, adult tissue homeostasis and pathophysiological processes such as cancer. In epithelial cancers TGFβ signaling can either suppress tumor growth or promote metastasis via the induction of a well-characterized epithelial-mesenchymal transition (EMT) program. We recently reported that PEAK1 kinase mediates signaling cross talk between TGFβ receptors and integrin/Src/MAPK pathways and functions as a critical molecular regulator of TGFβ-induced breast cancer cell proliferation, migration, EMT and metastasis. Here, we examined the breast cancer cell contexts in which TGFβ induces both EMT and PEAK1, and discovered this event to be unique to oncogene-transformed mammary epithelial cells and triple-negative breast cancer cells. Using the Cancer BioPortal database, we identified PEAK1 co-expressors across multiple malignancies that are also common to the TGFβ response gene signature (TBRS). We then used the ScanSite database to identify predicted protein-protein binding partners of PEAK1 and the PEAK1-TBRS co-expressors. Analysis of the Cytoscape interactome and Babelomics-derived gene ontologies for a novel gene set including PEAK1, CRK, ZEB1, IL11 and COL4A1 enabled us to hypothesize that PEAK1 may be regulating TGFβ-induced EMT via its interaction with or regulation of these other genes. In this regard, we have demonstrated that PEAK1 is necessary for TGFβ to induce ZEB1-mediated EMT in the context of fibronectin/ITGB3 activation. These studies and future mechanistic studies will pave the way toward identifying the context in which TGFβ blockade may significantly improve breast cancer patient outcomes. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 08/2015; 465(3). DOI:10.1016/j.bbrc.2015.08.071 · 2.30 Impact Factor
  • Source
    • "Moreover, naturally occurring somatic PIK3R1 mutations (I177N and E160*) and likely others disrupt p85α homodimerization, including mutations at P99 in PR1, R162*, frame shifts at Q153, D168, H180, V181, and L182 (Cheung et al., 2011; Cerami et al., 2012). Further, a patient-derived p85α mutant I133N that targets the PTEN interaction interface was identified using our speculative theoretical p85α:PTEN model. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The canonical action of the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3K) is to associate with the p110α catalytic subunit to allow stimuli-dependent activation of the PI3K pathway. We elucidate a p110α-independent role of homodimerized p85α in the positive regulation of PTEN stability and activity. p110α-free p85α homodimerizes via two intermolecular interactions (SH3:proline-rich region and BH:BH) to selectively bind unphosphorylated activated PTEN. As a consequence, homodimeric but not monomeric p85α suppresses the PI3K pathway by protecting PTEN from E3 ligase WWP2-mediated proteasomal degradation. Further, the p85α homodimer enhances the lipid phosphatase activity and membrane association of PTEN. Strikingly, we identified cancer patient-derived oncogenic p85α mutations that target the homodimerization or PTEN interaction surface. Collectively, our data suggest the equilibrium of p85α monomer–dimers regulates the PI3K pathway and disrupting this equilibrium could lead to disease development.
    eLife Sciences 07/2015; 4. DOI:10.7554/eLife.06866 · 9.32 Impact Factor
Show more