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

Publication ,  Journal Article
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 ...
Published in: Nat Commun
July 7, 2015

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 7, 2015

Volume

6

Start / End Page

7686

Location

England

Related Subject Headings

  • Treatment Outcome
  • Recurrence
  • Predictive Value of Tests
  • Pancreatic Neoplasms
  • Humans
  • Genomics
  • Gene Expression Regulation, Neoplastic
  • DNA
  • Biomarkers, Tumor
 

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Sausen, M., Phallen, J., Adleff, V., Jones, S., Leary, R. J., Barrett, M. T., … Velculescu, V. E. (2015). Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nat Commun, 6, 7686. https://doi.org/10.1038/ncomms8686
Sausen, Mark, Jillian Phallen, Vilmos Adleff, Siân Jones, Rebecca J. Leary, Michael T. Barrett, Valsamo Anagnostou, et al. “Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients.Nat Commun 6 (July 7, 2015): 7686. https://doi.org/10.1038/ncomms8686.
Sausen M, Phallen J, Adleff V, Jones S, Leary RJ, Barrett MT, et al. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nat Commun. 2015 Jul 7;6:7686.
Sausen, Mark, et al. “Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients.Nat Commun, vol. 6, July 2015, p. 7686. Pubmed, doi:10.1038/ncomms8686.
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. Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients. Nat Commun. 2015 Jul 7;6:7686.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

July 7, 2015

Volume

6

Start / End Page

7686

Location

England

Related Subject Headings

  • Treatment Outcome
  • Recurrence
  • Predictive Value of Tests
  • Pancreatic Neoplasms
  • Humans
  • Genomics
  • Gene Expression Regulation, Neoplastic
  • DNA
  • Biomarkers, Tumor