Breast Cancer Research and Treatment

, Volume 135, Issue 1, pp 79–91 | Cite as

Whole genome in vivo RNAi screening identifies the leukemia inhibitory factor receptor as a novel breast tumor suppressor

  • Elizabeth Iorns
  • Toby M. Ward
  • Sonja Dean
  • Anna Jegg
  • Dafydd Thomas
  • Nirupa Murugaesu
  • David Sims
  • Costas Mitsopoulos
  • Kerry Fenwick
  • Iwanka Kozarewa
  • Cristina Naceur-Lombarelli
  • Marketa Zvelebil
  • Clare M. Isacke
  • Christopher J. Lord
  • Alan Ashworth
  • H. James Hnatyszyn
  • Mark Pegram
  • Marc Lippman
Preclinical study

Abstract

Cancer is caused by mutations in oncogenes and tumor suppressor genes, resulting in the deregulation of processes fundamental to the normal behavior of cells. The identification and characterization of oncogenes and tumor suppressors has led to new treatment strategies that have significantly improved cancer outcome. The advent of next generation sequencing has allowed the elucidation of the fine structure of cancer genomes, however, the identification of pathogenic changes is complicated by the inherent genomic instability of cancer cells. Therefore, functional approaches for the identification of novel genes involved in the initiation and development of tumors are critical. Here we report the first whole human genome in vivo RNA interference screen to identify functionally important tumor suppressor genes. Using our novel approach, we identify previously validated tumor suppressor genes including TP53 and MNT, as well as several novel candidate tumor suppressor genes including leukemia inhibitory factor receptor (LIFR). We show that LIFR is a key novel tumor suppressor, whose deregulation may drive the transformation of a significant proportion of human breast cancers. These results demonstrate the power of genome wide in vivo RNAi screens as a method for identifying novel genes regulating tumorigenesis.

Keywords

Leukemia inhibitory factor receptor Tumor suppressor gene In vivo RNA interference screen Breast cancer 

Supplementary material

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Supplementary material 1 (DOC 154 kb)
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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Elizabeth Iorns
    • 1
  • Toby M. Ward
    • 1
  • Sonja Dean
    • 1
  • Anna Jegg
    • 1
  • Dafydd Thomas
    • 2
  • Nirupa Murugaesu
    • 3
  • David Sims
    • 3
  • Costas Mitsopoulos
    • 3
  • Kerry Fenwick
    • 3
  • Iwanka Kozarewa
    • 3
  • Cristina Naceur-Lombarelli
    • 3
  • Marketa Zvelebil
    • 3
  • Clare M. Isacke
    • 3
  • Christopher J. Lord
    • 3
  • Alan Ashworth
    • 3
  • H. James Hnatyszyn
    • 1
  • Mark Pegram
    • 1
  • Marc Lippman
    • 1
  1. 1.Department of Medicine, School of MedicineUniversity of MiamiMiamiUSA
  2. 2.Department of PathologyUniversity of Michigan Cancer CenterAnn ArborUSA
  3. 3.The Breakthrough Breast Cancer Research CentreThe Institute of Cancer ResearchLondonUK

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