Targeted next generation sequencing of endoscopic ultrasound acquired cytology from ampullary and pancreatic adenocarcinoma has the potential to aid patient stratification for optimal therapy selection

• DOI: 10.18632/oncotarget.9440
• Publication Date: 2016-05-22T02:37:45Z
• Authors: Ferga C. Gleeson; Sarah E. Kerr; Benjamin R. Kipp; Jesse S. Voss; Douglas M. Minot; Zheng Jin Tu; Michael R. Henry; Rondell P. Graham; George Vasmatzis; John C. Cheville; Konstantinos N. L...; Michael J. Levy
• Keywords: Endoscopic Ultrasound; Concordance; HRAS; Personalized Medicine

// Ferga C. Gleeson 1 , Sarah E. Kerr 2 Benjamin R. Kipp Jesse S. Voss Douglas M. Minot Zheng Jin Tu 3 Michael Henry Rondell P. Graham George Vasmatzis 4 John Cheville Konstantinos N. Lazaridis 1, J. Levy Division of Gastroenterology & Hepatology, Mayo Clinic Rochester, MN, USA Department Laboratory Medicine Pathology, Biomedical Statics Informatics, Health Sciences Research, Center for Individualized Medicine, Clinic, Correspondence to: Gleeson, email: [e-mail] Keywords: endoscopic ultrasound fine needle aspiration, pancreatic adenocarcinoma, targeted next-generation sequencing, mutation concordance, personalized medicine Received: April 04, 2016 Accepted: 24, Published: May 18, ABSTRACT Background Aims: Less than 10% registered drug intervention trials ductal adenocarcinoma (PDAC) include a biomarker stratification strategy. The ability to identify distinct subsets via aspiration (EUS FNA) molecular cytology could greatly aid clinical trial patient and offer predictive markers. We identified chemotherapy treatment naïve ampullary PDAC patients who underwent EUS FNA assess multigene mutational frequency diversity with surgical resection concordance assessment, where available. Methods: Following strict smear screening criteria, next generation sequencing (NGS) using 160 cancer gene panel was performed. Results: Complete achieved in 29 patients, whereby 83 pathogenic alterations were 21 genes. Cytology genotyping revealed that the majority mutations KRAS (93%), TP53 (72%), SMAD4 (31%), GNAS (10%). There 100% following alterations: KRAS, TP53, SMAD4, KMT2D, NOTCH2, MSH2, RB1, SMARCA4, PPP2R1A, PIK3R1, SCL7A8, ATM, FANCD2. Absolute 83%. Incremental GRIN2A, GATA3 KDM6A despite re-examination raw sequence reads corresponding specimens. Conclusions: NGS broad spectrum alterations. fidelity paired specimens suggests represents suitable surrogate may complement conventional criteria decision making therapies guide future driven therapeutic development.