Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.

摘要: Background Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung (NSCLC) represents 85% of all cancers. Understanding the molecular events in is essential to improve early diagnosis treatment for this disease. Methodology Principal Findings In an attempt identify novel NSCLC related genes, we performed a genome-wide screening chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization arrays on 32 radically resected tumor samples from stage I II patients. An integrative analysis tool was applied determine whether affects expression. We identified deletion 14q32.2-33 as common alteration (44%), which significantly influenced HSP90, residing 14q32. This correlated with better overall survival (P = 0.008), also longer patients whose tumors had low levels HSP90. extended three independent validation sets patients, confirmed HSP90 be 0.003, P 0.07 0.04). Furthermore, vitro inhibitor potent antiproliferative activity lines. Conclusions We suggest that targeting will have clinical impact