Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-12

AUTHORS

Mark Sausen, Jillian Phallen, Vilmos Adleff, Siân Jones, Rebecca J. Leary, Michael T. Barrett, Valsamo Anagnostou, Sonya Parpart-Li, Derek Murphy, Qing Kay Li, Carolyn A. Hruban, Rob Scharpf, James R. White, Peter J. O’Dwyer, Peter J. Allen, James R. Eshleman, Craig B. Thompson, David S. Klimstra, David C. Linehan, Anirban Maitra, Ralph H. Hruban, Luis A. Diaz, Daniel D. Von Hoff, Julia S. Johansen, Jeffrey A. Drebin, Victor E. Velculescu

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. More... »

PAGES

7686

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms8686

DOI

http://dx.doi.org/10.1038/ncomms8686

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1009287444

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26154128


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