Journal article
Sleeping Beauty mutagenesis reveals cooperating mutations and pathways in pancreatic adenocarcinoma
KM Mann, JM Ward, CCK Yew, A Kovochich, DW Dawson, MA Black, BT Brett, TE Sheetz, AJ Dupuy, DK Chang, AV Biankin, N Waddell, KS Kassahn, SM Grimmond, AG Rust, DJ Adams, NA Jenkins, NG Copeland
Proceedings of the National Academy of Sciences of the United States of America | Published : 2012
Abstract
Pancreatic cancer is one of the most deadly cancers affecting the Western world. Because the disease is highly metastatic and difficult to diagnosis until late stages, the 5-y survival rate is around 5%. The identification of molecular cancer drivers is critical for furthering our understanding of the disease and development of improved diagnostic tools and therapeutics. We have conducted a mutagenic screen using Sleeping Beauty (SB) in mice to identify new candidate cancer genes in pancreatic cancer. By combining SB with an oncogenic Kras allele, we observed highly metastatic pancreatic adenocarcinomas. Using two independent statistical methods to identify loci commonly mutated by SB in the..
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Awarded by National Institute of General Medical Sciences
Funding Acknowledgements
The authors thank Keith Rogers, Susan Rogers, and the Institute for Molecular and Cell Biology Histopathology Core. We thank Doug Melton for the Pdx1-Cre animals and Angela Chou, Anatomical Pathologist at the Garvan Institute of Medical Research, for performing the second blinded scoring for the tissue microarray. We also acknowledge Pearlyn Cheok, Nicole Lim, and Dorothy Chen for their help with tumor monitoring. This work was supported in part by the Biomedical Research Council, Agency for Science, Technology, and Research, Singapore; the National Health and Medical Research Council of Australia; the Queensland Government; the Cancer Council New South Wales; the Cancer Institute New South Wales; the Royal Australian College of Surgeons; the Australian Cancer Research Foundation; the St. Vincent's Clinic Foundation; the Avner Nahmani Pancreatic Cancer Foundation; and the R. T. Hall Trust.