Overall, there were more amplifications/deletions in these genes in metastases compared with primary tumors (8.6% loci altered vs. 4.5%, p < 0.001 Fishers exact, Table 2).
ARNT mRNA levels were increased ≥1.2-fold in metastatic compared with primary tumors in four patients (50%), and GDI2 in six (75%).
Analysis of the Oncomine database revealed an increase in CBX2 copy number in metastatic compared with primary pancreatic cancer (Supplementary Figure S4, P<0.001).
To analyze this in more detail, we tested if the functional groups altered in PDX models were similarly altered in metastases (compared with primary tumors).
The significant increase in the fraction of CD44+ and CD133+CD44+ cells in xenografts compared with primary tumours also underscores the important role of these sub-populations during tumourigenesis.
The data also show a higher frequency of E2F3 amplifications in metastases compared with primary UC and concordant increased E2F3 RNA expression in patients with E2F3 amplifications.
In an individual gene-wise comparison, there were more E2F3 amplifications in metastases compared with primary tumours (30% vs. 7%, p = 0.041 Fishers exact, Table 2 and Figure 1).
Lower expression was observed for WIF1 in metastases compared with primary tumors (U = 118, P = 0.004); for CXCL14, in metastasis compared with primary tumors (U = 138, P = 0.016); for CXCL14, in distant metastasis compared with all other tumor groups (U = 51, P = 0.013); and for NKX2-3, in distant metastasis compared with the other tumor groups (U = 45, P = 0.008) (Fig. 3).
However, it is still unknown whether EGFR status differs in metastases compared with primary NSCLC.
In addition, Rodriguez-Antona et al. [37] have reported, based on a large set of MTC cases, that EGFR is significantly overexpressed in metastases compared with primary tumors.
