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

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)79-91
Number of pages13
JournalBreast cancer research and treatment
Volume135
Issue number1
DOIs
StatePublished - Aug 1 2012

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Iorns, E., Ward, T. M., Dean, S., Jegg, A., Thomas, D., Murugaesu, N., Sims, D., Mitsopoulos, C., Fenwick, K., Kozarewa, I., Naceur-Lombarelli, C., Zvelebil, M., Isacke, C. M., Lord, C. J., Ashworth, A., Hnatyszyn, H. J., Pegram, M., & Lippman, M. (2012). Whole genome in vivo RNAi screening identifies the leukemia inhibitory factor receptor as a novel breast tumor suppressor. Breast cancer research and treatment, 135(1), 79-91. https://doi.org/10.1007/s10549-012-2068-7