| Literature DB >> 26154128 |
Mark Sausen1, Jillian Phallen1, Vilmos Adleff1, Siân Jones2, Rebecca J Leary1, Michael T Barrett3,4, Valsamo Anagnostou1, Sonya Parpart-Li2, Derek Murphy2, Qing Kay Li1, Carolyn A Hruban1, Rob Scharpf1, James R White1, Peter J O'Dwyer5, Peter J Allen6, James R Eshleman1,7, Craig B Thompson8, David S Klimstra9, David C Linehan10, Anirban Maitra1, Ralph H Hruban1,7, Luis A Diaz1, Daniel D Von Hoff3,11, Julia S Johansen12, Jeffrey A Drebin13, Victor E Velculescu1.
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.Entities:
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Year: 2015 PMID： 26154128 PMCID： PMC4634573 DOI： 10.1038/ncomms8686
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919