Whole genomes redefine the mutational landscape of pancreatic cancer
Article
Article Title | Whole genomes redefine the mutational landscape of pancreatic cancer |
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ERA Journal ID | 17479 |
Article Category | Article |
Authors | Waddell, Nicola (Author), Pajic, Marina (Author), Patch, Ann-Marie (Author), Chang, David K. (Author), Kassahn, Karin S. (Author), Bailey, Peter (Author), Johns, Amber L. (Author), Miller, David (Author), Nones, Katia (Author), Quek, Kelly (Author), Quinn, Michael C. J. (Author), Robertson, Alan J. (Author), Fadlullah, Muhammad Z. H. (Author), Bruxner, Tim J. C. (Author), Christ, Angelika N. (Author), Harliwong, Ivon (Author), Idrisoglu, Senel (Author), Manning, Suzanne (Author), Nourse, Craig (Author), Nourbakhsh, Ehsan (Author), Wani, Shivangi (Author), Wilson, Peter J. (Author), Markham, Emma (Author), Cloonan, Nicole (Author), Anderson, Matthew J. (Author), Fink, J. Lynn (Author), Holmes, Oliver (Author), Kazakoff, Stephen H. (Author), Leonard, Conrad (Author), Newell, Felicity (Author), Poudel, Barsha (Author), Song, Sarah (Author), Taylor, Darrin (Author), Waddell, Nick (Author), Wood, Scott (Author), Xu, Qinying (Author), Wu, Jianmin (Author), Pinese, Mark (Author), Cowley, Mark J. (Author), Lee, Hong C. (Author), Jones, Marc D. (Author), Nagrial, Adnan M. (Author), Humphris, Jeremy (Author), Chantrill, Lorraine A. (Author), Chin, Venessa (Author), Steinmann, Angela M. (Author), Mawson, Amanda (Author), Humphrey, Emily S. (Author), Colvin, Emily K. (Author), Chou, Angela (Author), Scarlett, Christopher J. (Author), Pinho, Andreia V. (Author), Giry-Laterriere, Marc (Author), Rooman, Ilse (Author), Samra, Jaswinder S. (Author), Kench, James G. (Author), Pettitt, Jessica A. (Author), Merrett, Neil D. (Author), Toon, Christopher (Author), Epari, Krishna (Author), Nguyen, Nam Q. (Author), Barbour, Andrew (Author), Zeps, Nikolajs (Author), Jamieson, Nigel B. (Author), Graham, Janet S. (Author), Niclou, Simone P. (Author), Bjerkvig, Rolf (Author), Grutzmann, Robert (Author), Aust, Daniela (Author), Hruban, Ralph H. (Author), Maitra, Anirban (Author), Iacobuzio-Donahue, Christine A. (Author), Wolfgang, Christopher L. (Author), Morgan, Richard A. (Author), Lawlor, Rita T. (Author), Corbo, Vincenzo (Author), Bassi, Claudio (Author), Falconi, Massimo (Author), Zamboni, Giuseppe (Author), Tortora, Giampaolo (Author), Tempero, Margaret A. (Author), Gill, Anthony J. (Author), Eshleman, James R. (Author), Pilarsky, Christian (Author), Scarpa, Aldo (Author), Musgrove, Elizabeth A. (Author), Pearson, John V. (Author), Biankin, Andrew V. (Author) and Grimmond, Sean M. (Author) |
Journal Title | Nature |
Journal Citation | 518 (7540), pp. 495-501 |
Number of Pages | 7 |
Year | 2015 |
Publisher | Nature Publishing Group |
Place of Publication | United Kingdom |
ISSN | 0028-0836 |
0090-0028 | |
0300-8746 | |
1476-4687 | |
Digital Object Identifier (DOI) | https://doi.org/10.1038/nature14169 |
Abstract | Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of DNA damage repair deficiency. Of 8 patients who received platinum therapy, 4 of 5 individuals with these measures of defective DNA maintenance responded. |
Keywords | pancreatic cancer; whole-genome sequencing; copy number variation |
ANZSRC Field of Research 2020 | 321103. Cancer genetics |
Public Notes | Files associated with this item cannot be displayed due to copyright restrictions. |
Byline Affiliations | University of Queensland |
University of New South Wales | |
Department of Health, New South Wales | |
Department of Health, Western Australia | |
Department of Health, South Australia | |
Department of Health, Queensland | |
University of Western Australia | |
University of Glasgow, United Kingdom | |
Norlux Neuro-Oncology Laboratory, Luxembourg | |
University of Bergen, Norway | |
Dresden University of Technology, Germany | |
Johns Hopkins University, United States | |
University of Texas at Austin, United States | |
Memorial Sloan Kettering Cancer Center, United States | |
University and Hospital Trust of Verona, Italy | |
University of Verona, Italy | |
University of California, United States | |
John Hopkins University, United States | |
Institution of Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q44x8/whole-genomes-redefine-the-mutational-landscape-of-pancreatic-cancer
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