Article Text
Abstract
Objective Pancreatic cysts are commonly detected in patients undergoing pancreatic imaging. Better approaches are needed to characterise these lesions. In this study we evaluated the utility of detecting mutant DNA in secretin-stimulated pancreatic juice.
Design Secretin-stimulated pancreatic juice was collected from the duodenum of 291 subjects enrolled in Cancer of the Pancreas Screening trials at five US academic medical centres. The study population included subjects with a familial predisposition to pancreatic cancer who underwent pancreatic screening, and disease controls with normal pancreata, chronic pancreatitis, sporadic intraductal papillary mucinous neoplasm (IPMN) or other neoplasms. Somatic GNAS mutations (reported prevalence ∼66% of IPMNs) were measured using digital high-resolution melt-curve analysis and pyrosequencing.
Results GNAS mutations were detected in secretin-stimulated pancreatic juice samples of 50 of 78 familial and sporadic cases of IPMN(s) (64.1%), 15 of 33 (45.5%) with only diminutive cysts (<5 mm), but none of 57 disease controls. GNAS mutations were also detected in five of 123 screened subjects without a pancreatic cyst. Among 97 subjects who had serial pancreatic evaluations, GNAS mutations detected in baseline juice samples predicted subsequent emergence or increasing size of pancreatic cysts.
Conclusion Duodenal collections of secretin-stimulated pancreatic juice from patients with IPMNs have a similar prevalence of mutant GNAS to primary IPMNs, indicating that these samples are an excellent source of mutant DNA from the pancreas. The detection of GNAS mutations before an IPMN is visible suggests that analysis of pancreatic juice has the potential to help in the risk stratification and surveillance of patients undergoing pancreatic screening.
- Pancreatic cancer
- intraductal papillary mucinous neoplasm
- pancreatic cyst
- pancreatic juice
- GNAS
- pancreas
- gastrointesinal endoscopy
- gastrointestinal ultrasound
- pancreatic disease
- pancreatic disorders
- endoscopic ultrasonography
- endoscopic retrograde pancreatography
- pancreatic tumours
- colonic polyps
- endoscopy
- oncogenes
- methylation
- gastrointestinal neoplasia
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- Pancreatic cancer
- intraductal papillary mucinous neoplasm
- pancreatic cyst
- pancreatic juice
- GNAS
- pancreas
- gastrointesinal endoscopy
- gastrointestinal ultrasound
- pancreatic disease
- pancreatic disorders
- endoscopic ultrasonography
- endoscopic retrograde pancreatography
- pancreatic tumours
- colonic polyps
- endoscopy
- oncogenes
- methylation
- gastrointestinal neoplasia
Footnotes
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Funding This work was supported by NIH grants (CA62924, R01CA120432, and RC2CA148376), the Lustgarten Foundation for Pancreatic Cancer Research, the Jimmy V Foundation, the Michael Rolfe Foundation, and Karp Family H H Metals, Inc Fund for Cancer Research Michael Hooven and Susan Spies. Material support: ChiRhoClin (secretin).
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Correction notice This article has been corrected since it was published Online First. The author affiliations have been amended.
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Competing interests MG and RHH have a licensing agreement with Myriad Genetics for the discovery of PALB2 as a pancreatic cancer susceptibility gene. There are no other conflicts of interest for any of the authors. Recombinant secretin was provided for this study but the companies involved had no part in the design of this study, analysis or interpretation of data or in the writing of this manuscript.
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Patient consent Obtained.
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Ethics approval Ethics approval was provided by Johns Hopkins Joint Committee for Clinical Investigation.
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Provenance and peer review Not commissioned; externally peer reviewed.