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Semaan, Alexander; Bernard, Vincent; Lee, Jaewon J; Wong, Justin W; Huang, Jonathan; Swartzlander, Daniel B; Stephens, Bret M; Monberg, Maria E; Weston, Brian R; Bhutani, Manoop S; Chang, Kyle; Scheet, Paul A; Maitra, Anirban; Jakubek, Yasminka A; Guerrero, Paola A
Clinical cancer research, 02/2021, Volume: 27, Issue: 4Journal Article
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. 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. 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. 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.
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