Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients.

Journal Article (Journal Article)

Pancreatic adenocarcinoma has the worst mortality of any solid cancer. In this study, to evaluate the clinical implications of genomic alterations in this tumour type, we perform whole-exome analyses of 24 tumours, targeted genomic analyses of 77 tumours, and use non-invasive approaches to examine tumour-specific mutations in the circulation of these patients. These analyses reveal somatic mutations in chromatin-regulating genes MLL, MLL2, MLL3 and ARID1A in 20% of patients that are associated with improved survival. We observe alterations in genes with potential therapeutic utility in over a third of cases. Liquid biopsy analyses demonstrate that 43% of patients with localized disease have detectable circulating tumour DNA (ctDNA) at diagnosis. Detection of ctDNA after resection predicts clinical relapse and poor outcome, with recurrence by ctDNA detected 6.5 months earlier than with CT imaging. These observations provide genetic predictors of outcome in pancreatic cancer and have implications for new avenues of therapeutic intervention.

Full Text

Duke Authors

Cited Authors

  • Sausen, M; Phallen, J; Adleff, V; Jones, S; Leary, RJ; Barrett, MT; Anagnostou, V; Parpart-Li, S; Murphy, D; Kay Li, Q; Hruban, CA; Scharpf, R; White, JR; O'Dwyer, PJ; Allen, PJ; Eshleman, JR; Thompson, CB; Klimstra, DS; Linehan, DC; Maitra, A; Hruban, RH; Diaz, LA; Von Hoff, DD; Johansen, JS; Drebin, JA; Velculescu, VE

Published Date

  • July 7, 2015

Published In

Volume / Issue

  • 6 /

Start / End Page

  • 7686 -

PubMed ID

  • 26154128

Pubmed Central ID

  • PMC4634573

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/ncomms8686


  • eng

Conference Location

  • England