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

BMC Cancer

Research Article

Jason Li¹  Natalie Thompson¹  David M Thomas²  Kenneth Opeskin³  SueAnne McLachlan⁴  Genni M Newnham⁴  Alexander Dobrovic⁵  Hongdo Do⁵  Matthew Conron⁶  Gavin M Wright⁷ 

[1] Bioinformatics Core Facility, Peter MacCallum Cancer Centre, (St Andrews Place), (3002), East Melbourne, Australia;Centre for Genomics and Predictive Medicine, Peter MacCallum Cancer Centre, (St Andrews Place), (3002), East Melbourne, Australia;Department of Anatomical Pathology, St Vincent's Hospital, (Victoria Pde), (3065), Melbourne, Australia;Department of Oncology, St Vincent's Hospital, (Victoria Pde), (3065), Melbourne, Australia;Department of Medicine, St Vincent's Hospital, The University of Melbourne, (Tin Alley), (3010), Melbourne, Australia;Department of Pathology, Peter MacCallum Cancer Centre, (St Andrews Place), (3002), East Melbournde, Australia;Department of Pathology, The University of Melbourne, (Tin Alley), (3010), Melbourne, Australia;Department of Respiratory Medicine, St Vincent's Hospital, (Victoria Pde), (3065), Melbourne, Australia;Department of Thoracic Surgery, St Vincent's Hospital, (Victoria Pde), (3065), Melbourne, Australia;

关键词: KRAS Mutation;    TP53 Mutation;    Copy Number Change;    Genomic Profile;    Large Cell Carcinoma;   

DOI  :  10.1186/1471-2407-11-93

 received in 2010-08-23, accepted in 2011-03-07,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsBoth 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.ResultsCombined 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.ConclusionsThese 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.

【 授权许可】

CC BY   
© Newnham et al; licensee BioMed Central Ltd. 2011