Hypermutation In Pancreatic Cancer

Australian Pancreatic Cancer Genome Initiative, Anirban Maitra, Christine A. Iacobuzio-Donahue, Richard D. Schulick

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)68-74.e2
JournalGastroenterology
Volume152
Issue number1
DOIs
StatePublished - Jan 1 2017

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Pancreatic Neoplasms
DNA Repair
Mutation
Immunotherapy
Patient Selection
Neoplasms
Clinical Trials
Genome
Therapeutics

Keywords

  • Cancer Genetics
  • Pancreatic Adenocarcinoma
  • Sequencing
  • Somatic Rearrangement

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Australian Pancreatic Cancer Genome Initiative, Maitra, A., Iacobuzio-Donahue, C. A., & Schulick, R. D. (2017). Hypermutation In Pancreatic Cancer. Gastroenterology, 152(1), 68-74.e2. https://doi.org/10.1053/j.gastro.2016.09.060

Hypermutation In Pancreatic Cancer. / Australian Pancreatic Cancer Genome Initiative; Maitra, Anirban; Iacobuzio-Donahue, Christine A.; Schulick, Richard D.

In: Gastroenterology, Vol. 152, No. 1, 01.01.2017, p. 68-74.e2.

Research output: Contribution to journalArticle

Australian Pancreatic Cancer Genome Initiative, Maitra, A, Iacobuzio-Donahue, CA & Schulick, RD 2017, 'Hypermutation In Pancreatic Cancer', Gastroenterology, vol. 152, no. 1, pp. 68-74.e2. https://doi.org/10.1053/j.gastro.2016.09.060
Australian Pancreatic Cancer Genome Initiative, Maitra A, Iacobuzio-Donahue CA, Schulick RD. Hypermutation In Pancreatic Cancer. Gastroenterology. 2017 Jan 1;152(1):68-74.e2. https://doi.org/10.1053/j.gastro.2016.09.060
Australian Pancreatic Cancer Genome Initiative ; Maitra, Anirban ; Iacobuzio-Donahue, Christine A. ; Schulick, Richard D. / Hypermutation In Pancreatic Cancer. In: Gastroenterology. 2017 ; Vol. 152, No. 1. pp. 68-74.e2.
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