Array comparative genomic hybridization of 18 pancreatic ductal adenocarcinomas and their autologous metastases

Background: Mortality rates of pancreatic cancer remain high, which is mainly due to advanced disease and metastasis. We hypothesized that DNA copy number alteration are enriched in metastatic cells compared to autologous primary tumors, which may inform on cancer-related pathways possibly serving as potential targets for specific therapies. We investigated 18 pancreatic ductal adenocarcinomas, including 39 lymph node and 5 distant metastases after surgical resection. Analysis was performed with array-based comparative genomic hybridization. Results: Metastases acquire a higher frequency of CNAs with the highest in distant metastasis (OM: median=42, LNM: median=23, PT: median=17). In LNM, gains were prevalent on chromosome bands 8q11.23-q24.3, 12q14.1, 17p12.1, 21q22.12, and losses on 3p21.31, 4p14, 8p23.3-p11.21,17p12-11.2. Genes on amplified regions are involved in cancer-related pathways such as WNT-signaling, also involved in metastasis. Conclusions: Pancreatic cancers show a high degree of intratumor heterogeneity, which could lead to resistance of chemotherapy and worse outcome. ACGH analysis reveals regions preferentially gained or lost in synchronous metastases encoding for genes involved in cancer-related pathways, which could lead to novel therapeutic opportunities. Array CGH experiment: DNA of 18 primary tumor cells (PT), 39 lymph node metastases (M) and 5 distant organ metastases (OM) of 18 pancreatic ductal adenocarcinomas (Cy3) versus control DNA (Cy5)