Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples

Alexander Semaan; Vincent Bernard; Jaewon J Lee; Justin W Wong; Jonathan Huang; Daniel B Swartzlander; Bret M Stephens; Maria E Monberg; Brian R Weston; Manoop S Bhutani; Kyle Chang; Paul A Scheet; Anirban Maitra; Yasminka A Jakubek; Paola A Guerrero

doi:10.1158/1078-0432.CCR-20-2667

Back

Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples

Journal article

Peer reviewed

Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples

Alexander Semaan, Vincent Bernard, Jaewon J Lee, Justin W Wong, Jonathan Huang, Daniel B Swartzlander, Bret M Stephens, Maria E Monberg, Brian R Weston, Manoop S Bhutani, …

Clinical cancer research, Vol.27(4), pp.1082-1093

02/15/2021

DOI: 10.1158/1078-0432.CCR-20-2667

PMID: 33188144

Files and links (1)

url

https://doi.org/10.1158/1078-0432.CCR-20-2667View

Published (Version of record) Open Access

Abstract

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.

Aged

Aged, 80 and over

Carcinoma, Pancreatic Ductal - genetics

Carcinoma, Pancreatic Ductal - mortality

Carcinoma, Pancreatic Ductal - pathology

Carcinoma, Pancreatic Ductal - therapy

DNA Copy Number Variations

DNA Mutational Analysis - methods

Endoscopic Ultrasound-Guided Fine Needle Aspiration

Feasibility Studies

Female

Genetic Heterogeneity

Genomics

Humans

Male

Middle Aged

Mutation

Pancreas - diagnostic imaging

Pancreas - pathology

Pancreatic Neoplasms - genetics

Pancreatic Neoplasms - mortality

Pancreatic Neoplasms - pathology

Pancreatic Neoplasms - therapy

Pilot Projects

Prognosis

Progression-Free Survival

Whole Exome Sequencing

Details

Title: Subtitle: Defining the Comprehensive Genomic Landscapes of Pancreatic Ductal Adenocarcinoma Using Real-World Endoscopic Aspiration Samples
Creators: Alexander Semaan - The University of Texas MD Anderson Cancer Center
Vincent Bernard - The University of Texas MD Anderson Cancer Center
Jaewon J Lee - The University of Texas MD Anderson Cancer Center
Justin W Wong - The University of Texas MD Anderson Cancer Center
Jonathan Huang - The University of Texas MD Anderson Cancer Center
Daniel B Swartzlander - The University of Texas MD Anderson Cancer Center
Bret M Stephens - The University of Texas MD Anderson Cancer Center
Maria E Monberg - The University of Texas MD Anderson Cancer Center
Brian R Weston - The University of Texas MD Anderson Cancer Center
Manoop S Bhutani - The University of Texas MD Anderson Cancer Center
Kyle Chang - The University of Texas MD Anderson Cancer Center
Paul A Scheet - The University of Texas MD Anderson Cancer Center
Anirban Maitra - The University of Texas MD Anderson Cancer Center
Yasminka A Jakubek - The University of Texas MD Anderson Cancer Center
Paola A Guerrero - The University of Texas MD Anderson Cancer Center
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.27(4), pp.1082-1093
DOI: 10.1158/1078-0432.CCR-20-2667
PMID: 33188144
ISSN: 1078-0432
eISSN: 1557-3265
Grant note: T32 CA009599 / NCI NIH HHS P50 CA221707 / NCI NIH HHS U01 CA196403 / NCI NIH HHS U01 CA200468 / NCI NIH HHS U54 CA096297 / NCI NIH HHS U54 CA096300 / NCI NIH HHS T32 CA217789 / NCI NIH HHS
Language: English
Date published: 02/15/2021
Academic Unit: Surgery
Record Identifier: 9985240893402771

Metrics

1 Record Views

25 Times Cited - Web of Science