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

Oncogene volume 34, pages 4238–4247 (2015)Cite this article

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Abstract

Using integrative genomics and functional screening, we identified coiled-coil domain containing 68 (CCDC68) as a novel putative tumor suppressor gene (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 single nucleotide polymorphism (SNP) variant (SNP rs1344011) that leads to exon skipping and generation of an unstable protein isoform CCDC68Δ69–114 in 31% of PDAC patients. Overexpression of full length CCDC68 (CCDC68wt) in PANC-1 and Hs.766T PDAC cell lines lacking CDCC68 expression decreased proliferation and tumorigenicity in scid mice. In contrast, the downregulation of endogenous CCDC68 in MIAPaca-2 cells increased tumor growth rate. These effects were not observed with the deletion-containing isoform, CCDC68Δ69–114.

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Acknowledgements

We thank the following people for assistance: James Ho (immunohistochemistry), Olga Ludkovksy (FISH), Ni Liu (PCR) and Dennis Wang (support in ICGC analysis). This study was supported by the Canadian Cancer Society Research Institute grant#700809, Canadian Institutes of Health Research grant MOP-49585 and the Ontario Ministry of Health and Long Term Care. N. Radulovich and K. Thu are Vanier Canada Graduate Scholars. Dr S. Sakashita is supported by the Terry Fox Foundation STIHR Program in Molecular Pathology of Cancer at CIHR (STP 53912). Dr Tsao is the M. Qasim Choksi Chair in Lung Cancer Translational Research.

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Authors and Affiliations

  1. Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada

    N Radulovich, L Leung, E Ibrahimov, R Navab, S Sakashita, C-Q Zhu, E Kaufman & M-S Tsao

  2. Department of Laboratory Medicine and Pathobiology Department, University of Toronto, Toronto, ON, Canada

    N Radulovich & M-S Tsao

  3. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    L Leung & M-S Tsao

  4. British Columbia Cancer Research Centre and Department of Pathology, University of British Columbia, Vancouver, BC, Canada

    W W Lockwood, K L Thu & W L Lam

  5. Department of Molecular Genetics, Banting & Best Department of Medical Research, University of Toronto, Toronto, ON, Canada

    Y Fedyshyn & J Moffat

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  1. N Radulovich
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Correspondence to M-S Tsao.

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Radulovich, N., Leung, L., Ibrahimov, E. et al. Coiled-coil domain containing 68 (CCDC68) demonstrates a tumor-suppressive role in pancreatic ductal adenocarcinoma. Oncogene 34, 4238–4247 (2015). https://doi.org/10.1038/onc.2014.357

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