Abstract 2462: Coiled-coil domain 68 (CCDC68) plays a tumor suppressive role in pancreatic adenocarcinoma

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is driven by somatic alterations. Recent studies revealed that most genetic alterations are represented by rare mutations in many genes that are either drivers or passengers of PDAC. Using integrative genomics and functional screenings we identified coiled-coil domain 68 (CCDC68) as a putative tumor suppressor (TSG) in PDAC. Combination of Q-RT-PCR and FISH analysis revealed CCDC68 allelic losses in 50% of PDAC cell lines and 44% of primary patient xenografts. 21% of PDAC cell lines and primary patient xenografts also showed decreased levels of CCDC68 mRNA and protein. We also report the discovery of an unstable novel alternate splice variant (SNP rs. 1344011) of CCDC68 expressed by 30% of PDAC patients. Overexpression of full length CCDC68 (CCDC68wt) in PANC-1 and Hs.766T cell lines significantly decreased their cell proliferation, anchorage-independent growth and in vivo tumorigenicity in scid mice. However, the overexpression of novel transcript CCDC68 variant did not affect the cell proliferation or tumorigenicity potential of PANC-1 cells. Finally, we identified that CCDC68 negatively regulates MAPK signalling independently of KRAS status. In conclusion, CCDC68 loss-of-function through copy loss, mRNA downregulation and truncated protein expression suppresses the tumorigenicity of PDAC cell lines suggesting that CCDC68 is a candidate novel TSG in PDAC. Citation Format: Nikolina Radulovich, Lisa Leung, Emin Ibrahimov, Roya Navab, Shingo Sakashita, William Lockwood, Kelsie Thu, Yaroslav Fedeshyn, Jason Moffat, Wan Lam, Ming Tsao. Coiled-coil domain 68 (CCDC68) plays a tumor suppressive role in pancreatic adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2462. doi:10.1158/1538-7445.AM2014-2462