Open Access Highly Accessed Research article

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

Genni M Newnham18*, Matthew Conron2, SueAnne McLachlan18, Alexander Dobrovic39, Hongdo Do39, Jason Li5, Kenneth Opeskin4, Natalie Thompson5, Gavin M Wright6 and David M Thomas7

Author Affiliations

1 Department of Oncology, St Vincent's Hospital, (Victoria Pde), Melbourne, (3065), Australia

2 Department of Respiratory Medicine, St Vincent's Hospital, (Victoria Pde), Melbourne, (3065), Australia

3 Department of Pathology, Peter MacCallum Cancer Centre, (St Andrews Place), East Melbourne, (3002), Australia

4 Department of Anatomical Pathology, St Vincent's Hospital, (Victoria Pde), Melbourne, (3065), Australia

5 Bioinformatics Core Facility, Peter MacCallum Cancer Centre, (St Andrews Place), East Melbourne, (3002), Australia

6 Department of Thoracic Surgery, St Vincent's Hospital, (Victoria Pde), Melbourne, (3065), Australia

7 Centre for Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, (St Andrews Place), East Melbourne, (3002), Australia

8 Department of Medicine, St Vincent's Hospital, The University of Melbourne, (Tin Alley), Melbourne, (3010), Australia

9 Department of Pathology, The University of Melbourne, (Tin Alley), Melbourne, (3010), Australia

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BMC Cancer 2011, 11:93  doi:10.1186/1471-2407-11-93

Published: 7 March 2011

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.