Journal Article

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

Fujiwara, Sho, Seike, Junro, Kanda, Mitsuro, Knight, Spencer, Lennon, Anne Marie, Hruban, Ralph H, Farrell, James, Lee, Jeffrey, Eshleman, James, Topazian, Mark, Syngal, Sapna, Canto, Marcia Irene, Goggins, Michael, Kamel, Ihab, Young, Angela, Borges, Michael

2013

Overview

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.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD
• Subject: Aged / Aged, 80 and over / Biomarkers, Tumor - genetics / Carcinoma, Pancreatic Ductal - diagnosis / Carcinoma, Pancreatic Ductal - genetics / Carcinoma, Pancreatic Ductal - pathology / Case-Control Studies / Chromogranins / colonic polyps / Cysts / Deoxyribonucleic acid / DNA / DNA, Neoplasm - genetics / Duodenum - metabolism / Early Detection of Cancer - methods / Early Diagnosis / endoscopic retrograde pancreatography / endoscopic ultrasonography / Endoscopy / Family medical history / Female / gastrointesinal endoscopy / gastrointestinal neoplasia / gastrointestinal ultrasound / Genetic Predisposition to Disease / GNAS / GTP-Binding Protein alpha Subunits, Gs - genetics / GTP-Binding Protein alpha Subunits, Gs - secretion / Hogs / Humans / intraductal papillary mucinous neoplasm / Male / methylation / Middle Aged / Mutation / Neoplasm Proteins - genetics / Neoplasm Proteins - secretion / oncogenes / pancreas / Pancreatic cancer / pancreatic cyst / Pancreatic Cyst - diagnosis / Pancreatic Cyst - genetics / Pancreatic Cyst - pathology / pancreatic disease / pancreatic disorders / pancreatic juice / Pancreatic Juice - metabolism / Pancreatic Neoplasms - diagnosis / Pancreatic Neoplasms - genetics / Pancreatic Neoplasms - pathology / pancreatic tumours / Rodents / Secretin / Studies / Surveillance / Tumors / Ultrasonic imaging