Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer

Kendall, J. T., Liu, Q. A., Bakleh, A., Krasnitz, A., Nguyen, K. C. Q., Lakshmi, B., Gerald, W., Powers, S., Mu, D. (October 2007) Oncogenic cooperation and coamplification of developmental transcription factor genes in lung cancer. Proc Natl Acad Sci U S A, 104 (42). pp. 16663-16668. ISSN 0027-8424 (Print)

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URL: https://www.ncbi.nlm.nih.gov/pubmed/17925434
DOI: 10.1073/pnas.0708286104

Abstract

We used high-resolution array analysis to discover a recurrent lung cancer amplicon located at 14q13.3. Low-level gain of this region was detected in 15% of lung cancer samples, and high-level amplification was detected in an additional 4% of samples. High-level focal amplification appears to be specific to lung cancers, because it was not detected in >500 samples of other tumor types. Mapping of the commonly amplified region revealed there are three genes in the core region, all of which encode transcription factors with either established lung developmental function (TTF1/NKX2-1, NKX2-8) or potential lung developmental function (PAX9). All three genes were overexpressed to varying degrees in amplified samples, although TTF1/NKX2-1 was not expressed in the squamous cancer subtype, consistent with previous reports. Remarkably, overexpression of any pairwise combination of these genes showed pronounced synergy in promoting the proliferation of immortalized human lung epithelial cells. Analysis of human lung cancer cell lines by both RNAi and ectopic overexpression further substantiates an oncogenic role for these transcription factors. These results, taken together with previous reports of oncogenic alterations of transcription factors involved in lung development (p63, CEBPA), suggest genetic alterations that directly interfere with transcriptional networks normally regulating lung development may be a more common feature of lung cancer than previously realized.

Item Type: Paper
Uncontrolled Keywords: gene amplification lung development lung oncogene TTF1 NKX2-8 PAX9 lineage addiction
Subjects: bioinformatics > genomics and proteomics > annotation > map annotation
bioinformatics > genomics and proteomics > Mapping and Rendering > Micro Array Data Rendering
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene amplification
diseases & disorders > cancer > cancer types > lung cancer
CSHL Authors:
Communities: CSHL labs > Krasnitz lab
CSHL labs > Powers lab
Depositing User: CSHL Librarian
Date: 16 October 2007
Date Deposited: 11 Nov 2011 16:54
Last Modified: 26 Jan 2017 20:44
PMCID: PMC2034240
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23060

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