title: Using next-generation sequencing to determine potential molecularly guided therapy options for patients with resectable pancreatic adenocarcinoma.
abstract: BACKGROUND
  Genomic sequencing technology may identify personalized treatment options for patients with pancreatic adenocarcinoma.
  
  
  METHODS
  The study was conducted using tissue specimens obtained from 2012 to 2014. Patients with resected pancreatic adenocarcinoma were identified. Next-generation sequencing was performed from paraffin-tumor blocks. Mutational profiles were reviewed to determine available targeted therapies and clinical trial eligibility.
  
  
  RESULTS
  Thirty patients were identified. The incidence of mutations was: Kirsten rat sarcoma viral oncogene homolong (KRAS) = 87%, tumor protein 53 (TP53) = 63%, cyclin-dependent kinase inhibitor 2A (CDKN2A) = 20%, Mothers Against Decapentaplegic Homolog 4 (SMAD4) = 20%, epidermal growth factor receptor (EGFR) = 7%. Multiple mutations were found in 73%. All CDKN2A mutations occurred in male patients (P = .06), and there was a trend toward younger patient age in this group (P = .13). Potential for Federal Drug Administration (FDA)-approved targeted therapies was identified in 8 of 30 (27%). In addition, 29 of 30 (97%) had mutations applicable for ongoing phase I or II clinical trials.
  
  
  CONCLUSIONS
  Next-generation sequencing of resected pancreatic adenocarcinoma specimens can determine common genetic mutations and identify patients who may be eligible for off-label use of targeted therapies or clinical trial enrollment.
authors.affiliation: General Surgery Residency Program, Grand Rapids Medical Education Partners/Michigan State University General Surgery Residency Program, 221 Michigan St, Suite 200A, Grand Rapids, 49503, MI, USA; Department of Surgery, Michigan State University College of Human Medicine, 221 Michigan St, Suite 200A, Grand Rapids, MI, 49503, USA. Electronic address: wrightgp@upmc.edu.
authors.forename: Gerald Paul
authors.initials: GP
authors.lastname: Wright
authors.affiliation: Spectrum Health Universal Biorepository, Grand Rapids, MI, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Chesla
authors.affiliation: General Surgery Residency Program, Grand Rapids Medical Education Partners/Michigan State University General Surgery Residency Program, 221 Michigan St, Suite 200A, Grand Rapids, 49503, MI, USA; Department of Surgery, Michigan State University College of Human Medicine, 221 Michigan St, Suite 200A, Grand Rapids, MI, 49503, USA; Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, MI, USA.
authors.forename: Mathew H
authors.initials: MH
authors.lastname: Chung
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000601:surgery*; D000367:Age Factors; D000368:Aged; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D062346:Molecular Medicine / Q000379:methods*; D009154:Mutation; D020360:Neoadjuvant Therapy; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000601:surgery*; D057285:Precision Medicine; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*; D012737:Sex Factors; D051901:Smad4 Protein / Q000235:genetics
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C117307:KRAS protein, human; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Genetic mutations; KRAS; Pancreas; Pancreatic cancer; TP53