Coiled-coil domain containing 68 (CCDC68) demonstrates a tumor suppressive role in pancreatic ductal adenocarcinoma

Using integrative genomics and functional screening we identified coiled-coil domain containing 68 (CCDC68) as a novel putative tumor suppressor (TSG) in pancreatic ductal adenocarcinoma (PDAC). CCDC68 allelic losses were documented in 48% of primary PDAC patient tumors, 50% of PDAC cell lines, and 30% of primary patient derived xenografts. We also discovered a SNP variant (SNP rs1344011) that leads to exon skipping and generation of an unstable protein isoform CCDC68Δ(69–114) in 31% of PDAC patients. Overexpression of full length CCDC68 (CCDC68(wt)) in PANC-1 and Hs.766T PDAC cell lines lacking CDCC68 expression decreased proliferation and tumorigenicity in scid mice. In contrast, downregulation of endogenous CCDC68 in MIAPaca-2 cells increased tumor growth rate. These effects were not observed with the deletion-containing isoform, CCDC68Δ(69–114). In conclusion, our results suggest that CCDC68 is a novel candidate TSG in PDAC.