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Cited by 164Pancreatic and Hepatic Oncology ResearchCancer Genomics and DiagnosticsPancreatitis Pathology and Treatment

Digital next-generation sequencing identifies low-abundance mutations in pancreatic juice samples collected from the duodenum of patients with pancreatic cancer and intraductal papillary mucinous neoplasms

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Yu, Jun, Sadakari, Yoshihiko, Shindo, Koji, Suenaga, Masaya, Brant, Aaron, Almario, Jose Alejandro Navarro, Borges, Michael, Barkley, Thomas +7 more·2017·Gut
DOI 10.1136/gutjnl-2015-311166PMC PMC5243915
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Abstract

Objective: Secretin-stimulated pancreatic juice contains DNA shed from cells lining the pancreatic ducts. Genetic analysis of this fluid may form a test to detect pancreatic ductal neoplasia. Design: We employed digital next-generation sequencing (‘digital NGS’) to detect low-abundance mutations in secretin-stimulated juice samples collected from the duodenum of subjects enrolled in Cancer of the Pancreas Screening studies at Johns Hopkins Hospital. For each juice sample, digital NGS necessitated 96 NGS reactions sequencing nine genes. The study population included 115 subjects (53 discovery, 62 validation) (1) with pancreatic ductal adenocarcinoma (PDAC), (2) intraductal papillary mucinous neoplasm (IPMN), (3) controls with non-suspicious pancreata. Results: Cases with PDAC and IPMN were more likely to have mutant DNA detected in pancreatic juice than controls (both p<0.0001); mutant DNA concentrations were higher in patients with PDAC than IPMN (p=0.003) or controls (p<0.001). TP53 and/or SMAD4 mutations were commonly detected in juice samples from patients with PDAC and were not detected in controls (p<0.0001); mutant TP53 / SMAD4 concentrations could distinguish PDAC from IPMN cases with 32.4% sensitivity, 100% specificity (area under the curve, AUC 0.73, p=0.0002) and controls (AUC 0.82, p<0.0001). Two of four patients who developed pancreatic cancer despite close surveillance had SMAD4/TP53 mutations from their cancer detected in juice samples collected over 1 year prior to their pancreatic cancer diagnosis when no suspicious pancreatic lesions were detected by imaging. Conclusions: The detection in pancreatic juice of mutations important for the progression of low-grade dysplasia to high-grade dysplasia and invasive pancreatic cancer may improve the management of patients undergoing pancreatic screening and surveillance.

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  • Blood remains the most commonly studied biospecimen for early detection, but many analytes are also present in other proximate samples, including pancreatic juice, stool, urine, saliva, and pancreatic cyst fluid.

    “In passing, it also needs to be stated that, although blood remains the most commonly studied biospecimen for early detection, many of the analytes are also present in other proximate samples, including pancreatic juice,53,54 stool,55 urine,56,57 saliva,58 and pancreatic cyst fluid.59”

    From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [53]

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Cited by

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Authors
Yu, J., Sadakari, Y., Shindo, K., Suenaga, M., Brant, A., Almario, J. A. N., Borges, M., Barkley, T., Fesharakizadeh, S., Ford, M., Hruban, R. H., Shin, E. J., Lennon, A. M., Canto, M. I., & Goggins, M.
Affiliations
Johns Hopkins University (US)
Corresponding author
Goggins, Michael
ORCID
Venue
Gut
Publisher
BMJ
Published
2016-07-18
Volume
66
Issue
9
Pages
1677-1687
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
DOI
10.1136/gutjnl-2015-311166
PMC
PMC5243915
OpenAlex
W2475585734
Cited by
164
References
11
Citations by year
2026: 11 · 2025: 7 · 2024: 13 · 2023: 14 · 2022: 14 · 2021: 16 · 2020: 23 · 2019: 22 · 2018: 24 · 2017: 19 · 2016: 1
FWCI
11.87
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Gut (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • Pancreatic Cancer Action Network
  • Lustgarten Foundation
  • Rolfe Pancreatic Cancer Foundation
  • National Institutes of Health (CA62924)
  • National Cancer Institute (R01CA120432, P50CA062924, R01CA176828, U01CA210170)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK089502)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
Keywords
pancreatic juice, secretin stimulation, liquid biopsy, pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, TP53 mutation, SMAD4 mutation, early cancer detection, pancreatic cancer screening, surveillance (medicine), duodenal juice
MeSH terms
Adult, Aged, Adenocarcinoma, Mucinous, Carcinoma, Papillary, Female, Genetic Testing, Humans, Male, Middle Aged, Mutation, Pancreas, Pancreatic Juice, Pancreatic Neoplasms, Predictive Value of Tests, Sensitivity and Specificity, Tumor Suppressor Protein p53, Sequence Analysis, DNA, Carcinoma, Pancreatic Ductal, Smad4 Protein

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