Reliable Detection of Somatic Mutations in Fine Needle Aspirates of XXXX With Next-generation Sequencing: Implications for Surgical Management.

@entity1 @entity788 @entity5 @entity14050 @entity19213
OBJECTIVE: To determine the feasibility of genotyping @entity788 via fine needle aspirates (FNAs). BACKGROUND: FNA is a common method of diagnosis for @entity788 , yet it has traditionally been considered inadequate for molecular studies due to the limited quantity of DNA derived from FNA specimens and @entity5 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 @entity5 tissue exhibited a concordance frequency of 100% for all driver genes present. In FNAs obtained from 17 @entity1 with unresectable disease, we identified at least 1 driver gene mutation in all @entity1 including actionable somatic mutations in @entity14050 and @entity19213 . The constellation of mutations identified in these @entity1 was different than that reported for resectable @entity788 , implying a biologic basis for presentation with locally advanced @entity788 . CONCLUSIONS: FNA sequencing is feasible and subsets of @entity1 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 @entity1 undergo neoadjuvant or a surgery-first approach based on their @entity5 genetics with the goal of utilizing @entity5 genomics in the clinical management of @entity788 .
