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Hypermutation In Pancreatic Cancer.

Authors :
Humphris JL
Patch AM
Nones K
Bailey PJ
Johns AL
McKay S
Chang DK
Miller DK
Pajic M
Kassahn KS
Quinn MC
Bruxner TJ
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
Source :
Gastroenterology [Gastroenterology] 2017 Jan; Vol. 152 (1), pp. 68-74.e2. Date of Electronic Publication: 2016 Nov 15.
Publication Year :
2017

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.<br /> (Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1528-0012
Volume :
152
Issue :
1
Database :
MEDLINE
Journal :
Gastroenterology
Publication Type :
Academic Journal
Accession number :
27856273
Full Text :
https://doi.org/10.1053/j.gastro.2016.09.060