Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins

Orit Rozenblatt-Rosen; Rahul C. Deo; Megha Padi; Guillaume Adelmant; Michael A. Calderwood; Thomas Rolland; Miranda Grace; Amelie Dricot; Manor Askenazi; Maria Tavares; Samuel J. Pevzner; Fieda Abderazzaq; Danielle Byrdsong; Anne-Ruxandra Carvunis; Alyce A. Chen; Jingwei Cheng; Mick Correll; Melissa Duarte; Changyu Fan; Mariet C. Feltkamp; Scott B. Ficarro; Rachel Franchi; Brijesh K. Garg; Natali Gulbahce; Tong Hao; Amy M. Holthaus; Robert James; Anna Korkhin; Larisa Litovchick; Jessica C. Mar; Theodore R. Pak; Sabrina Rabello; Renee Rubio; Yun Shen; Saurav Singh; Jennifer M. Spangle; Murat Tasan; Shelly Wanamaker; James T. Webber; Jennifer Roecklein-Canfield; Eric Johannsen; Albert-Laszlo Barabasi; Rameen Beroukhim; Elliott Kieff; Michael E. Cusick; David E. Hill; Karl Muenger; Jarrod A. Marto; John Quackenbush; Frederick P. Roth; James A. DeCaprio; Marc Vidal

doi:10.1038/nature11288

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Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins

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Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins

Orit Rozenblatt-Rosen, Rahul C. Deo, Megha Padi, Guillaume Adelmant, Michael A. Calderwood, Thomas Rolland, Miranda Grace, Amelie Dricot, Manor Askenazi, Maria Tavares, …

Nature (London), Vol.487(7408), pp.491-495

26/07/2012

DOI: https://doi.org/10.1038/nature11288

PMID: 22810586

Résumé

Multidisciplinary Sciences

Science & Technology

Science & Technology - Other Topics

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations(1). Genome sequencing efforts have identified numerous germline mutations, and large numbers of somatic genomic alterations, associated with a predisposition to cancer(2). However, it remains difficult to distinguish background, or 'passenger', cancer mutations from causal, or 'driver', mutations in these data sets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations(3). Here we test the hypothesis that genomic variations and tumour viruses may cause cancer through related mechanisms, by systematically examining host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways, such as Notch signalling and apoptosis, that go awry in cancer. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on a par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches increase the specificity of cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate the prioritization of cancer-causing driver genes to advance the understanding of the genetic basis of human cancer.

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Titre: Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins
Créateurs - sans rôle: Orit Rozenblatt-Rosen - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Rahul C. Deo - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Megha Padi - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Guillaume Adelmant - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Michael A. Calderwood - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Thomas Rolland - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Miranda Grace - Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
Amelie Dricot - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Manor Askenazi - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Maria Tavares - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Samuel J. Pevzner - Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA
Fieda Abderazzaq - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Danielle Byrdsong - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Anne-Ruxandra Carvunis - Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA
Alyce A. Chen - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Jingwei Cheng - Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA
Mick Correll - Dana Farber Canc Inst, CCCB, Dept Biostat & Computat Biol, Boston, MA 02215 USA
Melissa Duarte - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Changyu Fan - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Mariet C. Feltkamp - Leiden Univ, Med Ctr, Dept Med Microbiol, NL-2300 RC Leiden, Netherlands
Scott B. Ficarro - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Rachel Franchi - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Brijesh K. Garg - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Natali Gulbahce - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Tong Hao - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Amy M. Holthaus - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Robert James - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Anna Korkhin - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Larisa Litovchick - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Jessica C. Mar - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Theodore R. Pak - Univ Toronto, Donnelly Ctr, Toronto, ON M5G 1X5, Canada
Sabrina Rabello - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Renee Rubio - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Yun Shen - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Saurav Singh - Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
Jennifer M. Spangle - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Murat Tasan - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Shelly Wanamaker - Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA
James T. Webber - Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
Jennifer Roecklein-Canfield - Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA
Eric Johannsen - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Albert-Laszlo Barabasi - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Rameen Beroukhim - Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
Elliott Kieff - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Michael E. Cusick - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
David E. Hill - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Karl Muenger - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Jarrod A. Marto - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
John Quackenbush - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Frederick P. Roth - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
James A. DeCaprio - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Marc Vidal - Dana Farber Canc Inst, CCSB, Genom Anal Network Perturbat Ctr Excellence Genom, Boston, MA 02215 USA
Détails de publication: Nature (London), Vol.487(7408), pp.491-495
Éditeur: Springer Nature
Nombre de pages: 5
Note de subvention: Institute Sponsored Research funds from the Dana-Farber Cancer Institute Strategic Initiative F32GM095284 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) R01HG001715; R01CA093804; R01CA063113; P01CA050661; R01CA081135; R01CA066980; U01CA141583; R01CA131354; R01CA047006; R01CA085180; T32HL007208; K08HL098361; K08CA122833; F32GM095284; K25HG006031 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA K08CA122833 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P50HG004233 / Center of Excellence in Genomic Science (CEGS) from the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) Canada Excellence Research Chairs (CERC) Program, Canadian Institute for Advanced Research Fellowship and Ontario Research Fund K08HL098361 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 220020084 / James S. McDonnell Foundation R01HG001715 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI)
Identifiants: 99149498809311
Unité académique: Centre de Recherche en Biologie Cellulaire de Montpellier - CRBM
Langue: English
Type de ressource: Journal article