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Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer

Abstract

Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic profiling of 128 lung cancer cell lines and tumors revealed frequent focal DNA amplification at cytoband 14q13.3, a locus not amplified in other tumor types. The smallest region of recurrent amplification spanned the homeobox transcription factor TITF1 (thyroid transcription factor 1; also called NKX2-1), previously linked to normal lung development and function. When amplified, TITF1 exhibited increased expression at both the RNA and protein levels. Small interfering RNA (siRNA)-mediated knockdown of TITF1 in lung cancer cell lines with amplification led to reduced cell proliferation, manifested by both decreased cell-cycle progression and increased apoptosis. Our findings indicate that TITF1 amplification and overexpression contribute to lung cancer cell proliferation rates and survival and implicate TITF1 as a lineage-specific oncogene in lung cancer.

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Acknowledgements

We thank the SFGF for microarray manufacture, the SMD for database support, Ilana Galperin (Stanford Cytogenetics Laboratory) for assistance with FISH analysis and Eon Rios for assistance with FACS analysis. We also thank the members of the Pollack lab for helpful discussions. This work was supported in part by grants from the NIH: R01 CA97139 (JRP), T32 CA09151 (KAK), SPORE P50CA70907 (JDM), the DOD (JDM), the Vital, Anderson and Longenbaugh Foundations (JDM) and the Deutsche Krebshilfe: 10-2210-Pe4 (IP).

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Correspondence to J R Pollack.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Kwei, K., Kim, Y., Girard, L. et al. Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer. Oncogene 27, 3635–3640 (2008). https://doi.org/10.1038/sj.onc.1211012

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