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Hypermutation In Pancreatic Cancer.
- 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.)
- Subjects :
- Adult
Aged
Aged, 80 and over
DNA Mutational Analysis
Female
Genome
Humans
Male
Middle Aged
MutL Protein Homolog 1 genetics
MutS Homolog 2 Protein genetics
Proto-Oncogene Proteins p21(ras) genetics
Carcinoma, Pancreatic Ductal genetics
DNA Mismatch Repair genetics
Mutation
Pancreatic Neoplasms genetics
Transcriptome
Subjects
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