Hypermutation In Pancreatic Cancer
Copyright policy )Hypermutation In Pancreatic Cancer
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.
- The Kinghorn Cancer Centre Australia
- Catholic University of the Sacred Heart Italy
- University of Queensland Australia
- Johns Hopkins Medicine United States
- University of Newcastle Australia Australia
Adult, Male, DNA Mutational Analysis, cancer genetics, 610, Somatic Rearrangement, Somatic rearrangement, Carcinoma, Pancreatic Ductal/genetics, DNA Mismatch Repair/genetics, DNA Mismatch Repair, Proto-Oncogene Proteins p21(ras)/genetics, Proto-Oncogene Proteins p21(ras), XXXXXX - Unknown, Cancer Genetics, cancer, Sequencing, Humans, 2715 Gastroenterology, pancreas, Pancreatic Adenocarcinoma, Cancer genetics, genome, Aged, Aged, 80 and over, Genome, MutL Protein Homolog 1/genetics, Middle Aged, Pancreatic Neoplasms/genetics, Pancreatic Neoplasms, MutS Homolog 2 Protein, Pancreatic Adenocarcinoma; Sequencing; Somatic Rearrangement; Cancer Genetics, Mutation, Female, mutation, aged, 80 and over, MutL Protein Homolog 1, Transcriptome, Pancreatic adenocarcinoma, MutS Homolog 2 Protein/genetics, Carcinoma, Pancreatic Ductal
Adult, Male, DNA Mutational Analysis, cancer genetics, 610, Somatic Rearrangement, Somatic rearrangement, Carcinoma, Pancreatic Ductal/genetics, DNA Mismatch Repair/genetics, DNA Mismatch Repair, Proto-Oncogene Proteins p21(ras)/genetics, Proto-Oncogene Proteins p21(ras), XXXXXX - Unknown, Cancer Genetics, cancer, Sequencing, Humans, 2715 Gastroenterology, pancreas, Pancreatic Adenocarcinoma, Cancer genetics, genome, Aged, Aged, 80 and over, Genome, MutL Protein Homolog 1/genetics, Middle Aged, Pancreatic Neoplasms/genetics, Pancreatic Neoplasms, MutS Homolog 2 Protein, Pancreatic Adenocarcinoma; Sequencing; Somatic Rearrangement; Cancer Genetics, Mutation, Female, mutation, aged, 80 and over, MutL Protein Homolog 1, Transcriptome, Pancreatic adenocarcinoma, MutS Homolog 2 Protein/genetics, Carcinoma, Pancreatic Ductal
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