C Dutruel, F Bergmann, I Rooman, M Zucknick, D Weichenhan, L Geiselhart, T Kaffenberger, P S Rachakonda, A Bauer, N Giese, C Hong, H Xie, J F Costello, J Hoheisel, R Kumar, M Rehli, P Schirmacher, J Werner, C Plass, O Popanda, P Schmezer
Pancreatic ductal adenocarcinoma (PDAC) is usually incurable. Contrary to genetic mechanisms involved in PDAC pathogenesis, epigenetic alterations are ill defined. Here, we determine the contribution of epigenetically silenced genes to the development of PDAC. We analyzed enriched, highly methylated DNAs from PDACs, chronic pancreatitis (CP) and normal tissues using CpG island microarrays and identified WNK2 as a prominent candidate tumor suppressor gene being downregulated early in PDAC development. WNK2 was further investigated in tissue microarrays, methylation analysis of early pancreatic intraepithelial neoplasia (PanIN), mouse models for PDAC and pancreatitis, re-expression studies after demethylation, and cell growth assays using WNK2 overexpression...
June 26, 2014: Oncogene