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Integrated mutation, copy number and expression profiling in resectable non-small cell lung cancer

Author(s): Newnham Genni | Conron Matthew | McLachlan SueAnne | Dobrovic Alexander | Do Hongdo | Li Jason | Opeskin Kenneth | Thompson Natalie | Wright Gavin | Thomas David

Journal: BMC Cancer
ISSN 1471-2407

Volume: 11;
Issue: 1;
Start page: 93;
Date: 2011;
Original page

Abstract Background The aim of this study was to identify critical genes involved in non-small cell lung cancer (NSCLC) pathogenesis that may lead to a more complete understanding of this disease and identify novel molecular targets for use in the development of more effective therapies. Methods Both transcriptional and genomic profiling were performed on 69 resected NSCLC specimens and results correlated with mutational analyses and clinical data to identify genetic alterations associated with groups of interest. Results Combined analyses identified specific patterns of genetic alteration associated with adenocarcinoma vs. squamous differentiation; KRAS mutation; TP53 mutation, metastatic potential and disease recurrence and survival. Amplification of 3q was associated with mutations in TP53 in adenocarcinoma. A prognostic signature for disease recurrence, reflecting KRAS pathway activation, was validated in an independent test set. Conclusions These results may provide the first steps in identifying new predictive biomarkers and targets for novel therapies, thus improving outcomes for patients with this deadly disease.
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