Original articlePancreas, biliary tract, and liverMutant TP53 in Duodenal Samples of Pancreatic Juice From Patients With Pancreatic Cancer or High-Grade Dysplasia
Section snippets
Materials and Methods
All elements of this investigation were approved by The Johns Hopkins Medical Institutional Review Board and written informed consent was obtained from all patients. All authors had access to the study data and reviewed and approved the final manuscript.
Prevalence of TP53 Mutations in Pancreatic Intraepithelial Neoplasias, Intraductal Papillary Mucinous Neoplasms, and Ductal Adenocarcinomas
TP53 mutations were detected in 9.1% of intermediate-grade IPMNs, 17.8% of intermediate-grade PanINs (PanIN-2), 38.1% of high-grade IPMNs, 47.6% of PanIN-3, and 75% of 20 invasive ductal adenocarcinomas (one cancer had 2 mutations) (Table 1). No TP53 mutations were detected in low-grade PanINs (PanIN-1) or IPMNs.
Detection of Mutant TP53 in Duodenal Collections of Pancreatic Juice
We first evaluated the limit of detection of our digital HRM assay. Mutant TP53 reliably could detect 0.1% to 10% concentrations of mutant to wild-type DNA (Supplementary Figure 1).
We
Discussion
Our results indicate that mutant TP53 detected in duodenal collections of secretin-stimulated pancreatic juice may provide evidence that the pancreas contains either microscopic PanIN-3 IPMNs with high-grade dysplasia, or invasive pancreatic ductal adenocarcinoma. Mutant TP53 was detected in the pancreatic juice of only 1 of 102 individuals not known to have high-grade dysplasia, and that was a patient with a 6-cm IPMN with intermediate-grade dysplasia. The prevalence of mutant TP53 detected in
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Systematic review and meta-analysis: Diagnostic performance of DNA alterations in pancreatic juice for the detection of pancreatic cancer
2022, PancreatologyCitation Excerpt :The initial search identified 580 studies, of which 504 were excluded based on title and abstract. After full-text review, 41 studies were included: 32 concerning DNA mutations, 14 DNA methylations and five describing both [12–52] (Fig. 1). For each study, distinct collection methods and DNA analysis methods were reported.
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Conflicts of interest These authors disclose the following: Michael Goggins and Ralph Hruban have a licensing agreement with Myriad Genetics for the discovery of PALB2 as a pancreatic cancer susceptibility gene. The remaining authors disclose no conflicts.
None of the companies involved had any part in the design of this study, analysis or interpretation of data, or in the writing of this manuscript. The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and statistical analysis.
Funding Supported by National Institutes of Health grants (CA62924, R01CA120432, and RC2CA148376), the Lustgarten Foundation for Pancreatic Cancer Research, the Jimmy V Foundation, Susan Wojcicki and Dennis Troper, the Michael Rolfe Foundation, the Alan Graff Foundation, Karp Family H.H. Metals, Inc, Fund for Cancer Research, Michael Hooven and Susan Spies, and Hugh and Rachel Victor. Recombinant secretin was provided for this study by ChiRhoClin, Inc, and Repligen.