Expression signatures in lung cancer reveal a profile for EGFR-mutant tumours and identify selective PIK3CA overexpression by gene amplification

The development of targeted therapies creates a need to discriminate tumours accurately by their histological and genetic characteristics. Here, we aim to identify gene expression profiles and single markers that recapitulate the pathological and genetic background of non-small cell lung cancer (NSC...

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Bibliographic Details
Published in:The Journal of pathology 2008-02, Vol.214 (3), p.347-356
Main Authors: Angulo, B, Suarez-Gauthier, A, Lopez-Rios, F, Medina, PP, Conde, E, Tang, M, Soler, G, Lopez-Encuentra, A, Cigudosa, JC, Sanchez-Cespedes, M
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Biological and medical sciences
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Squamous Cell - genetics
Case-Control Studies
cDNA microarrays
Class I Phosphatidylinositol 3-Kinases
Cluster Analysis
EGFR
Gene Amplification
Gene Expression Profiling
Genes, ras
Genetic Markers
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Investigative techniques, diagnostic techniques (general aspects)
lung cancer
Lung Neoplasms - genetics
Medical sciences
Mutation
Oligonucleotide Array Sequence Analysis
Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques
Phosphatidylinositol 3-Kinases - genetics
PIK3CA
Pneumology
Receptor, Epidermal Growth Factor - genetics
Tumors of the respiratory system and mediastinum
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Summary:The development of targeted therapies creates a need to discriminate tumours accurately by their histological and genetic characteristics. Here, we aim to identify gene expression profiles and single markers that recapitulate the pathological and genetic background of non-small cell lung cancer (NSCLC). We performed cDNA microarray analysis on a series of 69 NSCLCs, with known mutation status for important genes, and six normal lung tissues. Unsupervised cluster analysis segregated normal lungs from lung tumours and lung tumours according to their histopathology and the presence of EGFR mutations. Several transcripts were highly overexpressed (by ~20 times) in squamous cell carcinomas (SCCs) relative to adenocarcinomas (ACs) and confirmed by immunohistochemistry in an independent cohort of 75 lung tumours. Expression of 13 genes constituted the most prominent hallmarks of EGFR-mutant tumours, including increased levels of proline dehydrogenase (PRODH) and down-regulation of X-box binding protein 1 (XBP1). No genes were differentially expressed, with a fold change >= 4 or
ISSN:0022-3417
1096-9896
DOI:10.1002/path.2267