TY - JOUR
T1 - Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples
AU - Semaan, Alexander
AU - Bernard, Vincent
AU - Lee, Jaewon J.
AU - Wong, Justin W.
AU - Huang, Jonathan
AU - Swartzlander, Daniel B.
AU - Stephens, Bret M.
AU - Monberg, Maria E.
AU - Weston, Brian R.
AU - Bhutani, Manoop S.
AU - Chang, Kyle
AU - Scheet, Paul A.
AU - Maitra, Anirban
AU - Jakubek, Yasminka A.
AU - Guerrero, Paola A.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/2/15
Y1 - 2021/2/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-20-2667
DO - 10.1158/1078-0432.CCR-20-2667
M3 - Article
C2 - 33188144
AN - SCOPUS:85101765956
SN - 1078-0432
VL - 27
SP - 1082
EP - 1093
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -