Hypermutation In Pancreatic Cancer

Humphris JL, Patch AM, Nones K, Bailey PJ, Johns AL, Mckay S, Chang DK, Miller DK, Pajic M, Kassahn KS, Quinn MCJ, Bruxner TJC, Christ AN, Harliwong I, Idrisoglu S, Manning S, Nourse C, Nourbakhsh E, Stone A, Wilson PJ, Anderson M, Fink JL, Holmes O, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Mead RS, Xu Q, Wu J, Pinese M, Cowley MJ, Jones MD, Nagrial AM, Chin VT, Chantrill LA, Mawson A, Chou A, Scarlett CJ, Pinho AV, Rooman I, Giry-Laterriere M, Samra JS, Kench JG, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Jamieson NB, Mckay CJ, Carter CR, Dickson EJ, Graham JS, Duthie F, Oien K, Hair J, Morton JP, Sansom OJ, Grützmann R, Hruban RH, Maitra A, Iacobuzio-Donahue CA, Schulick RD, Wolfgang CL, Morgan RA, Lawlor RT, Rusev B, Corbo V, Salvia R, Cataldo I, Tortora G, Tempero MA, Hofmann O, Eshleman JR, Pilarsky C, Scarpa A, Musgrove EA, Gill AJ, Pearson JV, Grimmond SM, Waddell N, Biankin AV (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Book Volume: 152

Pages Range: 68-74.e2

Journal Issue: 1

DOI: 10.1053/j.gastro.2016.09.060

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.

Authors with CRIS profile

Involved external institutions

Royal North Shore Hospital (RNSH) Australia (AU) University of Queensland Australia (AU) QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Garvan Institute of Medical Research Australia (AU) University Hospital of Verona / Azienda Ospedaliera Universitaria Integrata Verona (AOUI) Italy (IT) Johns Hopkins University (JHU) United States (USA) (US) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) Queen Elizabeth University Hospital United Kingdom (GB) Southern General Hospital United Kingdom (GB) University of Glasgow United Kingdom (GB) Glasgow Royal Infirmary (GRI) United Kingdom (GB) University of Verona / Università degli Studi di Verona Italy (IT) University of Western Australia (UWA) Australia (AU) Royal Adelaide Hospital Australia (AU) Fiona Stanley Hospital Australia (AU) Bankstown-Lidcombe Hospital Australia (AU)

How to cite

APA:

Humphris, J.L., Patch, A.-M., Nones, K., Bailey, P.J., Johns, A.L., Mckay, S.,... Biankin, A.V. (2017). Hypermutation In Pancreatic Cancer. Gastroenterology, 152(1), 68-74.e2. https://dx.doi.org/10.1053/j.gastro.2016.09.060

MLA:

Humphris, Jeremy L., et al. "Hypermutation In Pancreatic Cancer." Gastroenterology 152.1 (2017): 68-74.e2.

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