Hypermutation in pancreatic cancer

Humphris, J. L. et al. (2017) Hypermutation in pancreatic cancer. Gastroenterology, 152(1), 68-74.e2. (doi:10.1053/j.gastro.2016.09.060) (PMID:27856273)

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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.

Item Type:Articles
Additional Information:<br>Australian Pancreatic Cancer Genome Initiative.</br> <br>Funding support: National Health and Medical Research Council of Australia (NHMRC; 631701, 535903, 427601, 1112113) Queensland Government (NIRAP) University of Queensland Institute for Molecular Bioscience Australian Government: Department of Innovation, Industry, Science and Research (DIISR) Australian Cancer Research Foundation (ACRF) Cancer Council NSW: (SRP06-01, SRP11-01. ICGC) Cancer Institute NSW: (10/ECF/2-26; 06/ECF/1-24; 09/CDF/2-40; 07/CDF/1-03; 10/CRF/1-01, 08/RSA/1-15, 07/CDF/1-28, 10/CDF/2-26,10/FRL/2-03, 06/RSA/1-05, 09/RIG/1-02, 10/TPG/1-04, 11/REG/1-10, 11/CDF/3-26,13ECF1-46, 13/CDF/1-01) Garvan Institute of Medical Research. Avner Nahmani Pancreatic Cancer Foundation. Cancer Australia 1065022 Project Grant funding. R.T. Hall Trust Petre Foundation Jane Hemstritch in memory of Philip Hemstritch Gastroenterological Society of Australia (GESA) American Association for Cancer Research (AACR) Landon Foundation – INNOVATOR Award Royal Australasian College of Surgeons (RACS) Royal Australasian College of Physicians (RACP) Royal College of Pathologists of Australasia (RCPA) QIMR Berghofer Medical Research Institute Keith Boden Fellowship Italian Ministry of Research (Cancer Genome Project FIRB RBAP10AHJB) Associazione Italiana Ricerca Cancro (12182) Fondazione Italiana Malattie Pancreas – Ministero Salute (CUP_J33G13000210001) European Community Grant FP7 Cam-Pac Cam-Pac, Grant agreement no: 602783 National Institutes of Health (USA) grant CA62924.</br>
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bailey, Dr Peter and Oien, Dr Karin and Morton, Dr Jennifer and Biankin, Professor Andrew and Miller, Mr David and Musgrove, Dr Elizabeth and Duthie, Dr Fraser and Grimmond, Professor Sean and McKay, Mr Colin and Nourse, Dr Craig and Chang, Dr David and Graham, Dr Janet and Sansom, Professor Owen
Authors: Humphris, J. L., Patch, A.-M., Nones, K., Bailey, P. J., Johns, A. L., McKay, S., Chang, D. K., Miller, D. K., Pajic, M., Kassahn, K. S., Quinn, M. C.J., Bruxner, T. J.C., Christ, A. N., Harliwong, I., Idrisoglu, S., Manning, S., Nourse, C., Nourbakhsh, E., Stone, A., Wilson, P. J., Anderson, M., Fink, J. L., Holmes, O., Kazakoff, S., Leonard, C., Newell, F., Waddell, N., Wood, S., Mead, R. S., Xu, Q., Wu, J., Pinese, M., Cowley, M. J., Jones, M. D., Nagrial, A. M., Chin, V. T., Chantrill, L. A., Mawson, A., Chou, A., Scarlett, C. J., Pinho, A. V., Rooman, I., Giry-Laterriere, M., Samra, J. S., Kench, J. D., Merrett, N. D., Toon, C. W., Epari, K., Nguyen, N. Q., Barbour, A., Zeps, N., Jamieson, N. B., McKay, C. J., Carter, C. R., Dickson, E. J., Graham, J. S., Duthie, F., Oien, K., Hair, J., Morton, J. P., Sansom, O. J., Grutzman, R., Hruban, R. H., Maitra, A., Iacobuzio-Donahue, C. A., Schulick, R. D., Wolfgang, C. L., Morgan, R. A., Lawlor, R. T., Rusev, B., Corbo, V., Salvia, R., Cataldo, I., Tortora, G., Tempero, M. A., Hoffman, O., Eshleman, J. R., Pilarsky, C., Scarpa, A., Musgrove, E. A., Gill, A. J., Pearson, J. V., Grimmond, S. M., Waddell, N., and Biankin, A. V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Gastroenterology
Publisher:Elsevier
ISSN:0016-5085
ISSN (Online):1528-0012
Published Online:16 November 2016
Copyright Holders:Copyright © 2016 Elsevier
First Published:First published in Gastroenterology 152(1):68-74.e2
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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