Hypermutation in pancreatic cancer

Jeremy L. Humphris, Ann Marie Patch, Katia Nones, Peter J. Bailey, Amber L. Johns, Skye McKay, David K. Chang, David K. Miller, Marina Pajic, Karin S. Kassahn, Michael C. J. Quinn, Timothy J. C. Bruxner, Angelika N. Christ, Ivon Harliwong, Senel Idrisoglu, Suzanne Manning, Craig Nourse, Ehsan Nourbakhsh, Andrew Stone, Peter J. WilsonMatthew Anderson, J. Lynn Fink, Oliver Holmes, Stephen Kazakoff, Conrad Leonard, Felicity Newell, Nick Waddell, Scott Wood, Ronald S. Mead, Qinying Xu, Jianmin Wu, Mark Pinese, Mark J. Cowley, Marc D. Jones, Adnan M. Nagrial, Venessa T. Chin, Lorraine A. Chantrill, Amanda Mawson, Angela Chou, Christopher J. Scarlett, Andreia V. Pinho, Ilse Rooman, Marc Giry-Laterriere, Jaswinder S. Samra, James G. Kench, Neil D. Merrett, Christopher W. Toon, Krishna Epari, Nam Q. Nguyen, Andrew Barbour, Nikolajs Zeps, Nigel B. Jamieson, Colin J. McKay, C. Ross Carter, Euan J. Dickson, Janet S. Graham, Fraser Duthie, Karin Oien, Jane Hair, Jennifer P. Morton, Owen J. Sansom, Robert Grützmann, Ralph H. Hruban, Anirban Maitra, Christine A. Iacobuzio-Donahue, Richard D. Schulick, Christopher L. Wolfgang, Richard A. Morgan, Rita T. Lawlor, Borislav Rusev, Vincenzo Corbo, Roberto Salvia, Ivana Cataldo, Giampaolo Tortora, Margaret A. Tempero, Australian Pancreatic Cancer Genome Initiative, Oliver Hofmann, James R. Eshleman, Christian Pilarsky, Aldo Scarpa, Elizabeth A. Musgrove, Anthony J. Gill, John V. Pearson, Sean M. Grimmond, Nicola Waddell, Andrew V. Biankin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

165 Citations (Scopus)


Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer.

Original languageEnglish
Pages (from-to)68-74.e2
Number of pages9
Issue number1
Publication statusPublished - Jan 2017
Externally publishedYes


  • pancreatic adenocarcinoma
  • sequencing
  • somatic rearrangement
  • cancer genetics


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