循环肿瘤ctDNA在肿瘤和胰腺癌中的临床应用.pdfVIP

ARTICLE Received 27 Feb 2015 | Accepted 2 Jun 2015 | Published 7 Jul 2015 DOI: 10.1038/ncomms8686 Clinical implications of genomic alterations in the tumour and circulation of pancreatic cancer patients 1,w 1 1 ˆ 2 1,w 3,4 Mark Sausen , Jillian Phallen , Vilmos Adleff , Sian Jones , Rebecca J. Leary , Michael T. Barrett , 1 2 2 1 1 1 Valsamo Anagnostou , Sonya Parpart-Li , Derek Murphy , Qing Kay Li , Carolyn A. Hruban , Rob Scharpf , 1 5 6 1,7 8 James R. White , Peter J. O’Dwyer , Peter J. Allen , James R. Eshleman , Craig B. Thompson , 9 10 1 1,7 1 David S. Klimstra , David C. Linehan , Anirban Maitra , Ralph H. Hruban , Luis A. Diaz, Jr. , Daniel D. Von Hoff3,11, Julia S. Johansen12, Jeffrey A. Drebin13 Victor E. Velculescu1 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