publication . Article . Other literature type . 2017

Hypermutation In Pancreatic Cancer

Humphris, Jeremy L.; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J.; Johns, Amber L.; McKay, Skye; Chang, David K.; Miller, David K.; Pajic, Marina; Kassahn, Karin S.; ...
  • Published: 01 Jan 2017
  • Country: India
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 ...
Subjects
free text keywords: Gastroenterology, MLH1, DNA mismatch repair, Cancer research, DNA repair, Pancreatic cancer, medicine.disease, medicine, Somatic hypermutation, Mutation, medicine.disease_cause, MSH2, Cancer, business.industry, business
Funded by
NHMRC| Research Fellowship - Grant ID:427601
Project
  • Funder: National Health and Medical Research Council (NHMRC) (NHMRC)
  • Project Code: 427601
  • Funding stream: NHMRC Research Fellowships
,
NHMRC| International Cancer Genome Consortium
Project
  • Funder: National Health and Medical Research Council (NHMRC) (NHMRC)
  • Project Code: 631701
  • Funding stream: NHMRC Strategic Awards
,
EC| CAM-PAC
Project
CAM-PAC
Integrative Analysis of Gene Functions in Cellular and Animal Models of Pancreatic Cancer
  • Funder: European Commission (EC)
  • Project Code: 602783
  • Funding stream: FP7 | SP1 | HEALTH
,
NHMRC| Molecular markers of phenotype, therapeutic responsiveness and prognosis in human cancers.
Project
  • Funder: National Health and Medical Research Council (NHMRC) (NHMRC)
  • Project Code: 535903
  • Funding stream: Programs
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