Abstract
Purpose:
Most patients with pancreatic ductal adenocarcinoma (PDAC) present with surgically unresectable cancer. As a result, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the most common biospecimen source available for diagnosis in treatment-naïve patients. Unfortunately, these limited samples are often not considered adequate for genomic analysis, precluding the opportunity for enrollment on precision medicine trials.
Experimental design:
Applying an epithelial cell adhesion molecule (EpCAM)-enrichment strategy, we show the feasibility of using real-world EUS-FNA for in-depth, molecular-barcoded, whole-exome sequencing (WES) and somatic copy-number alteration (SCNA) analysis in 23 patients with PDAC.
Results:
Potentially actionable mutations were identified in >20% of patients. Further, an increased mutational burden and higher aneuploidy in WES data were associated with an adverse prognosis. To identify predictive biomarkers for first-line chemotherapy, we developed an SCNA-based complexity score that was associated with response to platinum-based regimens in this cohort.
Conclusions:
Collectively, these results emphasize the feasibility of real-world cytology samples for in-depth genomic characterization of PDAC and show the prognostic potential of SCNA for PDAC diagnosis.