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Type: Journal article
Title: Hypermutation in pancreatic cancer
Author: Humphris, J.
Patch, A.
Nones, K.
Bailey, P.
Johns, A.
McKay, S.
Chang, D.
Miller, D.
Pajic, M.
Kassahn, K.
Quinn, M.
Bruxner, T.
Christ, A.
Harliwong, I.
Idrisoglu, S.
Manning, S.
Nourse, C.
Nourbakhsh, E.
Stone, A.
Wilson, P.
et al.
Citation: Gastroenterology, 2017; 152(1):68-74.e2
Publisher: American Gastroenterological Association Institute
Issue Date: 2017
ISSN: 0016-5085
Statement of
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. Wilson, Matthew 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
Abstract: 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.
Keywords: Cancer Genetics; Pancreatic Adenocarcinoma; Sequencing; Somatic Rearrangement
Rights: © 2017 by the AGA Institute
RMID: 0030059527
DOI: 10.1053/j.gastro.2016.09.060
Grant ID:
Appears in Collections:Medicine publications

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