@article{f350c76e77c547228f2bbd3fb6e4f159,
title = "Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients",
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.",
author = "Mark Sausen and Jillian Phallen and Vilmos Adleff and Si{\^a}n Jones and Leary, {Rebecca J.} and Barrett, {Michael T.} and Valsamo Anagnostou and Sonya Parpart-Li and Derek Murphy and Li, {Qing Kay} and Hruban, {Carolyn A.} and Rob Scharpf and White, {James R.} and O'Dwyer, {Peter J.} and Allen, {Peter J.} and Eshleman, {James R.} and Thompson, {Craig B.} and Klimstra, {David S.} and Linehan, {David C.} and Anirban Maitra and Hruban, {Ralph H.} and Diaz, {Luis A.} and {Von Hoff}, {Daniel D.} and Johansen, {Julia S.} and Drebin, {Jeffrey A.} and Velculescu, {Victor E.}",
note = "Funding Information: We thank S. Angiuoli, L. Kann, C. McCord and B. Vogelstein for technical assistance with next-generation sequencing analyses; and R. Posner and M. Aziz for their assistance with pancreatic tumour cell nuclei purification. This work was supported by the American Association for Cancer Research Stand Up To Cancer–Dream Team Translational Cancer Research Grant, the SU2C-DCS International Translational Cancer Research Dream Team Grant (SU2C-AACR-DT1415), the Commonwealth Foundation, NIH grants CA121113 and CA62924, FasterCures Research Acceleration Award, Swim Across America, D. Troper and S. Wojcicki. Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research.",
year = "2015",
month = jul,
day = "7",
doi = "10.1038/ncomms8686",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}