Mutation Analysis of Pancreatic Juice and Plasma for the Detection of Pancreatic Cancer
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Published:2023-08-23
Issue:17
Volume:24
Page:13116
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Levink Iris J. M.1ORCID, Jansen Maurice P. H. M.2, Azmani Zakia3, van IJcken Wilfred3ORCID, van Marion Ronald4ORCID, Peppelenbosch Maikel P.1ORCID, Cahen Djuna L.1ORCID, Fuhler Gwenny M.1ORCID, Bruno Marco J.1
Affiliation:
1. Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands 2. Department of Medical Oncology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands 3. Center for Biomics, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands 4. Department of Pathology, Erasmus MC, University Medical Center, 3015 GD Rotterdam, The Netherlands
Abstract
Molecular profiling may enable earlier detection of pancreatic cancer (PC) in high-risk individuals undergoing surveillance and allow for personalization of treatment. We hypothesized that the detection rate of DNA mutations is higher in pancreatic juice (PJ) than in plasma due to its closer contact with the pancreatic ductal system, from which pancreatic cancer cells originate, and higher overall cell-free DNA (cfDNA) concentrations. In this study, we included patients with pathology-proven PC or intraductal papillary mucinous neoplasm (IPMN) with high-grade dysplasia (HGD) from two prospective clinical trials (KRASPanc and PACYFIC) for whom both PJ and plasma were available. We performed next-generation sequencing on PJ, plasma, and tissue samples and described the presence (and concordance) of mutations in these biomaterials. This study included 26 patients (25 PC and 1 IPMN with HGD), of which 7 were women (27%), with a median age of 71 years (IQR 12) and a median BMI of 23 kg/m2 (IQR 4). Ten patients with PC (40%) were (borderline) resectable at baseline. Tissue was available from six patients (resection n = 5, biopsy n = 1). A median volume of 2.9 mL plasma (IQR 1.0 mL) and 0.7 mL PJ (IQR 0.1 mL, p < 0.001) was used for DNA isolation. PJ had a higher median cfDNA concentration (2.6 ng/μL (IQR 4.2)) than plasma (0.29 ng/μL (IQR 0.40)). A total of 41 unique somatic mutations were detected: 24 mutations in plasma (2 KRAS, 15 TP53, 2 SMAD4, 3 CDKN2A 1 CTNNB1, and 1 PIK3CA), 19 in PJ (3 KRAS, 15 TP53, and 1 SMAD4), and 8 in tissue (2 KRAS, 2 CDKN2A, and 4 TP53). The mutation detection rate (and the concordance with tissue) did not differ between plasma and PJ. In conclusion, while the concentration of cfDNA was indeed higher in PJ than in plasma, the mutation detection rate was not different. A few cancer-associated genetic variants were detected in both biomaterials. Further research is needed to increase the detection rate and assess the performance and suitability of plasma and PJ for PC (early) detection.
Funder
Gastrostart Dutch Organisation for Scientific Research Dutch Cancer Foundation
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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