Newnham et al. BMC Cancer 2011, 11:93 http://www.biomedcentral.com/1471-2407/11/93 R E S E A R C H A R T I C L E Open Access Integrated mutation, copy number and expression profiling in resectable non-small cell lung cancer Genni M Newnham1,8*, Matthew Conron2, SueAnne McLachlan1,8, Alexander Dobrovic3,9, Hongdo Do3,9, Jason Li 5 , Kenneth Opeskin4, Natalie Thompson5, Gavin M Wright6, David M Thomas7 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. Background Non-small cell lung cancer (NSCLC) is the commonest cause of cancer death in Western communities. Current treatments offer the potential of cure only to the small number of patients who present with early stage NSCLC, whilst outcomes for those with advanced disease remain poor. Recent advances including adjuvant chemotherapy and targeted biological therapies have lead to modest improvements in survival for small subgroups of patients. Clearly new treatment approaches are required to substan- tially improve outcome. As has been the case for other tumour types, molecular profiling techniques have the potential to provide benefit through improved understand- ing of disease pathogenesis, identification of subgroups in whom current therapies are most likely to be effective and in the development of novel therapies. * Correspondence: Genni.Newnham@svhm.org.au 1Department of Oncology, St Vincent’s Hospital, (Victoria Pde), Melbourne, (3065), Australia Full list of author information is available at the end of the article Genetic heterogeneity is a feature of NSCLC, with vary- ing combinations of multiple molecular alterations contri- buting to tumour development [1]. A key challenge for high-throughput molecular profiling techniques is to dis- tinguish between genes whose expression is altered directly by heritable changes in gene function and those where changes are an inevitable down-stream conse- quence of primary changes to genes directly involved in disease pathogenesis. Correlation of transcriptional and genomic data allows more focussed analysis of the large number of genetic alterations identified by molecular pro- filing. This study incorporates the results of both tran- scriptional and genomic profiling for clinically relevant subgroups of NSCLC to identify genes of potential predic- tive or pathogenic importance in this deadly disease. Methods Samples After obtaining institutional ethics approval, patients with stage I-IIIA NSCLC seen by the St Vincent’s Hospital © 2011 Newnham et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.