Table 4 Details of genes located in regions of genomic difference with concordant differences in expression levels between AC and SCC Symbol Gene Name TP73L CSTA ATP1B3 VNN2 ABCC5 UPK1B Tumour protein 73-like Cystatin A (Stefin A) ATPase, Na+/K+ transporting, beta 3 polypeptide Vanin 2 ATP-binding cassette, subfamily C, member 5 Uroplakin 1B RBP1 Retinol binding protein 1 SGK Serum/glucocorticoid regulated kinase TNFSF10/ Tumour necrosis factor (ligand) superfamily, member 10/TNF-related apoptosis-inducing TRAIL ligand TNFAIP3 Tumour necrosis factor, alpha-induced protein 33 PFN2 Profilin 2 PLOD2 B3GNT5 EIF4A2 MAP3K4 PDCD10 SEP1 NCK1 GPR126 LSAMP DZIP3 PIK3A2 WASF-1 CITED2/ MRG1 Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 5 Eukaryotic translation initiation factor 4A, isoform 2 Mitogen activated protein kinase kinase kinase 4 Programmed cell death 10 5’-3’ exoribonuclease 1 NCK adaptor protein G-protein coupled receptor 126 Limbic system-associated membrane protein Zinc finger DAZ interacting protein Phosphoinositide-3-kinase, catalytic, alpha WAS protein family, member 1 CBP/P300-interacting transactivator, with GLU/ASP rich carboxy-terminal domain 2/ Melanocyte specific gene 1 related gene 1 Cytoband Difference in expression (log2 SCC-AC) 3q28 2.94 3q21 2.27 3q23 1.46 6q23-q24 1.34 3q27 1.28 3q13.3- 1.12 q21 3q23 1.12 6q23 1.06 3q26 1.05 6q23 0.84 3q25.1- 0.83 25.2 3q23-q24 0.80 3q28 0.80 3q28 0.66 6q26 0.59 3q26.1 0.58 3q25- 0.54 q26.1 3q21 0.52 6q24.1 0.52 3q13.2- 0.49 q21 3q13.13 0.45 3q26.3 0.44 6q21-q22 0.44 6q23.3 -0.63 Newnham et al. BMC Cancer 2011, 11:93 http://www.biomedcentral.com/1471-2407/11/93 and gene regulation. As previously reported, we identified amplification and over-expression of COX2 in KRAS mutant tumours. KRAS mutant tumours did not demon- strate mutations in EGFR consistent with previous reports in both NSCLC and colon carcinoma which suggest that KRAS mutations predict resistance to EGFR antagonists [29,38-41]. Several reports link NCAM1 to Ras-dependent activation of ERK MAPK’s [42,43]. Reduced copy number and expression of NCAM1 in tumours bearing KRAS mutations, as seen in our data, has not previously been reported. Further research into a KRAS mutation profile may yield simple and reliable immunohistochemical mar- kers of KRAS mutation, thereby significantly reduce the cost of determining KRAS status in clinical practice. The gene expression profile observed in ‘metastatic’ tumours is consistent with a growing body of literature implicating deregulated protein synthesis in the develop- ment and metastatic potential of human cancers [44,45]. Increased mRNA translation is a critical downstream function of many cancer related genes, and many gene pro- ducts with roles in metastasis are not mutated but inappro- priately expressed in malignant cells (e.g. VEGF, c-Myc, fos, Her2Neu, PDGF) [18]. Opportunities for therapeutic inter- vention currently in development include oncolytic viruses that require deregulated protein translation for their replica- tion [18], or agents that inhibit mTOR, an integral factor in protein translation (eg. temsirolimus (CCI-779), everolimus (RAD001) and deforolimus (AP23573)). While the small number of recurrences and deaths due to NSCLC in our tumour-set makes it difficult to draw strong conclusions, transcriptional profiles linked to tumour recurrence suggest KRAS pathway activation. This may be due to a higher proportion of AC and LCC vs. SCC in the ‘recurrent’ group. Other regions of copy number change demonstrate genomic gains in the region of c-Myc and losses in the region of p16 (INK4a, CDNK2A) in recurrent or non-survivor tumours, sup- porting a prognostic association of the Myc:CDNK2A Page 8 of 11 P value 1.69 E-10 3.42 E-8 1.06 E-6 1.00 E-4 2.2 E-4 3.3 E-3 1.98 E-3 1.3 E-4 1.7 E-4 5.0 E-4 8.1 E-3 6.7 E-3 2.8 E-3 4.1 E-3 1.8 E-3 2.9 E-3 8.2 E-3 7.3 E-3 1.7 E-3 3.4 E-3 4.9 E-3 9.2 E-3 8.3 E-3 8.0 E-3