| Literature DB >> 27856273 |
Jeremy L Humphris1, Ann-Marie Patch2, Katia Nones2, Peter J Bailey3, Amber L Johns1, Skye McKay1, David K Chang4, David K Miller5, Marina Pajic6, Karin S Kassahn7, Michael C J Quinn2, Timothy J C Bruxner8, Angelika N Christ8, Ivon Harliwong8, Senel Idrisoglu8, Suzanne Manning8, Craig Nourse9, Ehsan Nourbakhsh8, Andrew Stone1, Peter J Wilson8, Matthew Anderson8, J Lynn Fink8, Oliver Holmes2, Stephen Kazakoff2, Conrad Leonard2, Felicity Newell2, Nick Waddell8, Scott Wood2, Ronald S Mead10, Qinying Xu2, Jianmin Wu1, Mark Pinese1, Mark J Cowley6, Marc D Jones11, Adnan M Nagrial1, Venessa T Chin1, Lorraine A Chantrill12, Amanda Mawson1, Angela Chou13, Christopher J Scarlett14, Andreia V Pinho1, Ilse Rooman1, Marc Giry-Laterriere1, Jaswinder S Samra15, James G Kench16, Neil D Merrett17, Christopher W Toon1, Krishna Epari18, Nam Q Nguyen19, Andrew Barbour20, Nikolajs Zeps21, Nigel B Jamieson22, Colin J McKay23, C Ross Carter23, Euan J Dickson23, Janet S Graham24, Fraser Duthie25, Karin Oien25, Jane Hair26, Jennifer P Morton27, Owen J Sansom27, Robert Grützmann28, Ralph H Hruban29, Anirban Maitra29, Christine A Iacobuzio-Donahue29, Richard D Schulick30, Christopher L Wolfgang30, Richard A Morgan29, Rita T Lawlor31, Borislav Rusev31, Vincenzo Corbo31, Roberto Salvia31, Ivana Cataldo31, Giampaolo Tortora32, Margaret A Tempero33, Oliver Hofmann34, James R Eshleman29, Christian Pilarsky35, Aldo Scarpa31, Elizabeth A Musgrove36, Anthony J Gill37, John V Pearson2, Sean M Grimmond38, Nicola Waddell39, Andrew V Biankin40.
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.Entities:
Keywords: Cancer Genetics; Pancreatic Adenocarcinoma; Sequencing; Somatic Rearrangement
Mesh：
Substances：
Year: 2016 PMID： 27856273 DOI： 10.1053/j.gastro.2016.09.060
Source DB: PubMed Journal: Gastroenterology ISSN： 0016-5085 Impact factor: 22.682