Research Article: Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma

Date Published: July 27, 2010

Publisher: Public Library of Science

Author(s): William W. Lockwood, Raj Chari, Bradley P. Coe, Kelsie L. Thu, Cathie Garnis, Chad A. Malloff, Jennifer Campbell, Ariane C. Williams, Dorothy Hwang, Chang-Qi Zhu, Timon P. H. Buys, John Yee, John C. English, Calum MacAulay, Ming-Sound Tsao, Adi F. Gazdar, John D. Minna, Stephen Lam, Wan L. Lam, William Pao

Abstract: William Lockwood and colleagues show that the focal amplification of a gene, BRF2, on Chromosome 8p12 plays a key role in squamous cell carcinoma of the lung.

Partial Text: Lung cancer is the most common cause of cancer deaths worldwide [1],[2]. It is projected that by 2020, lung cancer will be the fifth most lethal entity among all diseases [3]. Improvement in survival has been very modest. Less than 16% of lung cancer patients survive 5 y or more [2], owing to late diagnosis and a paucity of effective therapies.

In summary, we show here that the focal amplification of Chromosome 8p12, one of the most frequent amplification events in NSCLC, plays a key role in squamous cell lineage specificity of the disease. Through the integration of genetic and gene expression data for >330 clinical tumor specimens in conjunction with functional cell model studies, we identified BRF2 as the target of this amplification and a cell lineage-specific oncogene, the only such oncogene described for lung SqCC to date. In addition, we highlight the oncogenic potential of BRF2 for the first time and associate its activation with increased Pol III activity, RNA processing, and resultant cell growth potential.



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