title: Reliable Detection of Somatic Mutations in Fine Needle Aspirates of Pancreatic Cancer With Next-generation Sequencing: Implications for Surgical Management.
abstract: OBJECTIVE
  To determine the feasibility of genotyping pancreatic tumors via fine needle aspirates (FNAs).
  
  
  BACKGROUND
  FNA is a common method of diagnosis for pancreatic cancer, yet it has traditionally been considered inadequate for molecular studies due to the limited quantity of DNA derived from FNA specimens and tumor heterogeneity.
  
  
  METHODS
  In vitro mixing studies were performed to deduce the minimum cellularity needed for genetic analysis. DNA from both simulated FNAs and clinical FNAs was sequenced. Mutational concordance was determined between simulated FNAs and that of the resected specimen.
  
  
  RESULTS
  Limiting dilution studies indicated that mutations present at allele frequencies as low as 0.12% are detectable. Comparison of simulated FNAs and matched tumor tissue exhibited a concordance frequency of 100% for all driver genes present. In FNAs obtained from 17 patients with unresectable disease, we identified at least 1 driver gene mutation in all patients including actionable somatic mutations in ATM and MTOR. The constellation of mutations identified in these patients was different than that reported for resectable pancreatic cancers, implying a biologic basis for presentation with locally advanced pancreatic cancer.
  
  
  CONCLUSIONS
  FNA sequencing is feasible and subsets of patients may harbor actionable mutations that could potentially impact therapy. Moreover, preoperative FNA sequencing has the potential to influence the timing of surgery relative to systemic therapy. FNA sequencing opens the door to clinical trials in which patients undergo neoadjuvant or a surgery-first approach based on their tumor genetics with the goal of utilizing cancer genomics in the clinical management of pancreatic cancer.
authors.affiliation: *Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD †Department of Pathology ‡Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD §Department of Radiation Oncology and Molecular Radiation Sciences, The Johns Hopkins University School of Medicine, Baltimore, MD ¶Department of Gastroenterology and Hepatology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Saunders
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Weiss
authors.forename: John L
authors.initials: JL
authors.lastname: Cameron
authors.forename: Avani
authors.initials: A
authors.lastname: Dholakia
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Wild
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Shin
authors.forename: Mouen A
authors.initials: MA
authors.lastname: Khashab
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: O'Broin-Lennon
authors.forename: Syed Z
authors.initials: SZ
authors.lastname: Ali
authors.forename: Daniel
authors.initials: D
authors.lastname: Laheru
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
mesh_terms: D001483:Base Sequence; D044963:Biopsy, Fine-Needle; D004273:DNA, Neoplasm / Q000032:analysis; D060005:Genotyping Techniques; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D015203:Reproducibility of Results
chemical_list: D004273:DNA, Neoplasm