• Vicente Valero, Tyler J Saunders, Jin He, Matthew J Weiss, John L Cameron, Avani Dholakia, Aaron T Wild, Eun Ji Shin, Mouen A Khashab, Anne Marie O'Broin-Lennon, Syed Z Ali, Daniel Laheru, Ralph H Hruban, Christine A Iacobuzio-Donahue, Joseph M Herman, and Christopher L Wolfgang.
• *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.
• Ann. Surg. 2016 Jan 1;263(1):153-61.

ObjectiveTo determine the feasibility of genotyping pancreatic tumors via fine needle aspirates (FNAs).BackgroundFNA 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.MethodsIn 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.ResultsLimiting 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.ConclusionsFNA 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.

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