Newnham et al. BMC Cancer 2011, 11:93 http://www.biomedcentral.com/1471-2407/11/93 Page 4 of 11 1 3 5 7 9 11 13 15 17 19 21 Figure 1 Plot of average standardised copy number at each BAC for AC and SCC samples. X axis: BAC location along genome. Y axis: average standardised copy number. was also more frequent in SCC than AC samples (p = 0.004). When analysing all samples, no relationship was found between 3q amplification and TP53 mutation (p = 0.99). However, when analysing SCC and AC separately, a statistically significant relationship between TP53 muta- tion and 3q amplification was detected in AC samples, with amplification of 3q being significantly more common in TP53 mutant cancers (1/8 and 4/10 samples with 3q amplification in TP53 wild-type (wt) and mutant AC groups respectively, p = 0.027). Both TP53 mutant and wt samples more frequently demonstrated copy number loss at the TP53 locus (17p13) than gain (11/18 and 9/12 sam- ples in TP53 mutant and wt groups respectively). Adenocarcinomas were screened for EGFR and KRAS mutations. Small numbers of EGFR mutant tumours limited detailed analysis. Good quality genomic profiles were available for only 5 tumours with EGFR mutation and no significant differences were seen between the profiles of EGFR mutant and non-mutant tumours. Genomic profiles were available for 8 KRAS mutant tumours, 31 wt and 16 tumours with unknown KRAS mutation status (untested SCC samples). In averaged copy number charts, KRAS mutant tumours showed a predilection for losses of 1p36.32-p13.2, 6q11.1-q27, 11p13-11q13.2 and 11q21-12p13.1 and gains of 1q21.1- q43 (Figure 2). Associations with metastasis, tumour recurrence and NSCLC-specific survival To investigate the notion of inherent metastatic poten- tial, molecular profiles of large (>4 cm) non-metastatic tumours and small (<2 cm) metastatic (nodal or distant) tumours were compared. Genomic profiles of 3 ‘meta- static’ and 8 ‘non-metastatic’ tumours revealed some dif- ferences in the magnitude of copy number changes, without regions of clear difference between the two groups. There was no correlation between genomic changes and tumour recurrence or survival. There were differences in the magnitude of gene copy number changes at 7p, 8q, 9p, 15q and 17p in recurrent com- pared to non-recurrent tumours. Contained within these regions are the MYC oncogene (8q), as well as TP53 (17p), and the CDKN2A locus (containing p14(ARF) and p16 tumour suppressor genes (9p) (TSG’s)). Transcriptional Analysis Histotype comparisons Ranking the genes by moderated t-statistics and selecting a p value cut-off of <0.005, 310 genes with differential