Nuclear Factor I/B is an Oncogene in Small Cell Lung Cancer

Small cell lung cancer (SCLC) is an aggressive cancer often diagnosed only after it has metastasized to distant sites (Meuwissen and Berns 2005; Cooper and Spiro 2006). Despite the need to better understand this disease, SCLC remains poorly characterized at the molecular and genomic levels (Forgacs et al. 2001; Pleasance et al. 2010). Using a genetically-engineered mouse model of SCLC driven by conditional deletion of Trp53 and Rb1 in the lung (Jonkers et al. 2001; Vooijs et al. 2002; Meuwissen et al. 2003; Sage et al. 2003), 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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Dooley AL, Winslow MM, Chiang DY, Banerji S, Stransky N, Dayton TL, Snyder EL, Senna S, Whittaker CA, Bronson RT, Crowley D, Barretina J, Garraway L, Meyerson M, Jacks T