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Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts.

ABSTRACT: 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.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.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.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.

SUBMITTER: Kanda M

PROVIDER: S-EPMC3893110 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts.

Kanda Mitsuro M Knight Spencer S Topazian Mark M Syngal Sapna S Farrell James J Lee Jeffrey J Kamel Ihab I Lennon Anne Marie AM Borges Michael M Young Angela A Fujiwara Sho S Seike Junro J Eshleman James J Hruban Ralph H RH Canto Marcia Irene MI Goggins Michael M

Gut 20120802 7

<h4>Objective</h4>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.<h4>Design</h4>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 fa ...[more]

PMID: 22859495

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Project description:The analysis of secretin-stimulated pancreatic fluid is being evaluated as an approach to improve the early detection of pancreatic cancer and pancreatic precursor neoplasms. The method of pancreatic fluid sampling may have a significant impact on tumor marker measurements. The aim of this study was to compare concentrations of mutant DNA in pancreatic fluid from patients who had samples collected from both the pancreatic duct and duodenal lumen.Thirty-six participants enrolled in the Cancer of the Pancreas Screening studies at Johns Hopkins Hospital who had secretin-stimulated pancreatic fluid collected from the duodenum during endoscopic ultrasound (EUS) and from the pancreatic duct during subsequent endoscopic retrograde cholangiopancreatography. Mutant KRAS and GNAS DNA concentrations were measured in pancreatic fluid samples using digital high-resolution melt-curve analysis and pyrosequencing and were related total DNA concentrations in these samples.Thirty-four patients had subtle parenchymal abnormalities by EUS; seven had small pancreatic cysts; none had pancreatic cancer. KRAS mutations were detected in 29 of 36 (80.6%) pancreatic duct fluid samples. Of these 29 patients, 23 had mutations detected in their duodenal fluid (79.3%). Patients with detectable pancreatic fluid but not duodenal fluid KRAS mutations had lower average pancreatic duct fluid KRAS mutation concentrations (P=0.01). Patients with KRAS or GNAS mutations detected in pancreatic fluid but not duodenal fluid had higher total DNA concentrations in their duodenal compared with pancreatic fluid (P=0.03). KRAS and GNAS mutation concentrations were higher in pancreatic duct fluid samples than in matching duodenal fluid samples (for KRAS: 2.62 vs. 0.39%, P<0.0001).KRAS and GNAS mutation concentrations are significantly lower in secretin-stimulated pancreatic fluid samples collected from the duodenum compared with samples collected from the pancreatic duct. Efforts to improve the purity of pancreatic fluid collections from the duodenum could improve the detection of mutations arising from the pancreas.

Dataset Information

Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts.

Publications

Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts.

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