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Nat Commun. 2015 Jul 7;6:7686. doi: 10.1038/ncomms8686.

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

Author information

1
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
2
Personal Genome Diagnostics Inc., Baltimore, Maryland 21224, USA.
3
1] The Translational Genomics Research Institute, Scottsdale, Arizona 85004, USA. [2] Mayo Clinic Arizona, Scottsdale, Arizona 85054, USA.
4
Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA.
5
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, USA.
6
1] The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. [2] Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
7
Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
8
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
9
School of Medicine and Dentistry, University of Rochester, Rochester, New York, 14642, USA.
10
1] The Translational Genomics Research Institute, Scottsdale, Arizona 85004, USA. [2] Virginia Piper Cancer Center, Scottsdale Healthcare, Scottsdale, Arizona 85258, USA.
11
Department of Oncology and Medicine, Herlev Hospital, University of Copenhagen, Copenhagen 2730, Denmark.
12
Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Abstract

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.

PMID:
26154128
PMCID:
PMC4634573
DOI:
10.1038/ncomms8686
[Indexed for MEDLINE]
Free PMC Article
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