Nuclear factor I/B is an oncogene in small cell lung cancer
- Alison L. Dooley1,
- Monte M. Winslow1,
- Derek Y. Chiang2,3,6,
- Shantanu Banerji2,3,
- Nicolas Stransky2,
- Talya L. Dayton1,
- Eric L. Snyder1,
- Stephanie Senna1,
- Charles A. Whittaker1,
- Roderick T. Bronson4,
- Denise Crowley1,
- Jordi Barretina2,3,
- Levi Garraway2,3,
- Matthew Meyerson2,3 and
- Tyler Jacks1,5,7
- 1David H. Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
- 2The Broad Institute, Cancer Program, Cambridge, Massachusetts 02142, USA;
- 3Department of Medical Oncology, Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA;
- 4Department of Pathology, Tufts University School of Medicine and Veterinary Medicine, North Grafton, Massachusetts 01536, USA;
- 5Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Abstract
Small cell lung cancer (SCLC) is an aggressive cancer often diagnosed after it has metastasized. Despite the need to better understand this disease, SCLC remains poorly characterized at the molecular and genomic levels. Using a genetically engineered mouse model of SCLC driven by conditional deletion of Trp53 and Rb1 in the lung, we identified several frequent, high-magnitude focal DNA copy number alterations in SCLC. We uncovered amplification of a novel, oncogenic transcription factor, Nuclear factor I/B (Nfib), in the mouse SCLC model and in human SCLC. Functional studies indicate that NFIB regulates cell viability and proliferation during transformation.
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Footnotes
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↵7 Corresponding author.
E-mail tjacks{at}mit.edu.
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.2046711.
- Received March 1, 2011.
- Accepted May 31, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
