Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts
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...
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| Published in | Gut Vol. 62; no. 7; pp. 1024 - 1033 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
BMJ Publishing Group Ltd and British Society of Gastroenterology
01.07.2013
BMJ Publishing Group LTD |
| Subjects | |
| Online Access | Get full text |
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| 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. |
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| AbstractList | 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 â^¼66% 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 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.OBJECTIVEPancreatic 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.DESIGNSecretin-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.RESULTSGNAS 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.CONCLUSIONDuodenal 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. 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. ObjectivePancreatic 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.DesignSecretin-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 similar to 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 (<5mm), 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.ConclusionDuodenal 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 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. |
| Author | 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 |
| AuthorAffiliation | 7 University of California at Los Angeles 6 Dana Farber Cancer Institute 1 Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions 2 Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions 3 Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions 4 Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions 8 MD Anderson Cancer Center 5 Mayo Clinic |
| AuthorAffiliation_xml | – name: 3 Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions – name: 7 University of California at Los Angeles – name: 8 MD Anderson Cancer Center – name: 5 Mayo Clinic – name: 6 Dana Farber Cancer Institute – name: 4 Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions – name: 2 Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions – name: 1 Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions |
| Author_xml | – sequence: 1 givenname: Mitsuro surname: Kanda fullname: Kanda, Mitsuro email: mgoggins@jhmi.edu organization: Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 2 givenname: Spencer surname: Knight fullname: Knight, Spencer email: mgoggins@jhmi.edu organization: Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 3 givenname: Mark surname: Topazian fullname: Topazian, Mark email: mgoggins@jhmi.edu organization: Mayo Clinic, Baltimore, Maryland, USA – sequence: 4 givenname: Sapna surname: Syngal fullname: Syngal, Sapna email: mgoggins@jhmi.edu organization: Dana Farber Cancer Institute, Boston, Massachusetts, USA – sequence: 5 givenname: James surname: Farrell fullname: Farrell, James email: mgoggins@jhmi.edu organization: University of California at Los Angeles, Los Angeles, California, USA – sequence: 6 givenname: Jeffrey surname: Lee fullname: Lee, Jeffrey email: mgoggins@jhmi.edu organization: MD Anderson Cancer Center, Houston, Texas, USA – sequence: 7 givenname: Ihab surname: Kamel fullname: Kamel, Ihab email: mgoggins@jhmi.edu organization: Departments of Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 8 givenname: Anne Marie surname: Lennon fullname: Lennon, Anne Marie email: mgoggins@jhmi.edu organization: Departments of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 9 givenname: Michael surname: Borges fullname: Borges, Michael email: mgoggins@jhmi.edu organization: Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 10 givenname: Angela surname: Young fullname: Young, Angela email: mgoggins@jhmi.edu organization: Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 11 givenname: Sho surname: Fujiwara fullname: Fujiwara, Sho email: mgoggins@jhmi.edu organization: Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 12 givenname: Junro surname: Seike fullname: Seike, Junro email: mgoggins@jhmi.edu organization: Departments of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 13 givenname: James surname: Eshleman fullname: Eshleman, James email: mgoggins@jhmi.edu organization: Departments of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 14 givenname: Ralph H surname: Hruban fullname: Hruban, Ralph H email: mgoggins@jhmi.edu organization: Departments of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 15 givenname: Marcia Irene surname: Canto fullname: Canto, Marcia Irene email: mgoggins@jhmi.edu organization: Departments of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA – sequence: 16 givenname: Michael surname: Goggins fullname: Goggins, Michael email: mgoggins@jhmi.edu organization: Departments of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/22859495$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions Copyright: 2013 Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions |
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| DOI | 10.1136/gutjnl-2012-302823 |
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| Keywords | gastrointestinal ultrasound pancreatic juice oncogenes endoscopy intraductal papillary mucinous neoplasm pancreatic cyst colonic polyps endoscopic retrograde pancreatography pancreatic disorders endoscopic ultrasonography Pancreatic cancer methylation pancreas GNAS gastrointesinal endoscopy pancreatic disease gastrointestinal neoplasia pancreatic tumours |
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| Snippet | Objective Pancreatic cysts are commonly detected in patients undergoing pancreatic imaging. Better approaches are needed to characterise these lesions. In this... Pancreatic cysts are commonly detected in patients undergoing pancreatic imaging. Better approaches are needed to characterise these lesions. In this study we... ObjectivePancreatic cysts are commonly detected in patients undergoing pancreatic imaging. Better approaches are needed to characterise these lesions. In this... |
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| SubjectTerms | 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 |
| Title | Mutant GNAS detected in duodenal collections of secretin-stimulated pancreatic juice indicates the presence or emergence of pancreatic cysts |
| URI | http://gut.bmj.com/content/62/7/1024.full https://api.istex.fr/ark:/67375/NVC-6SHLRZMJ-R/fulltext.pdf https://www.ncbi.nlm.nih.gov/pubmed/22859495 https://www.proquest.com/docview/1779435535 https://www.proquest.com/docview/1365990622 https://www.proquest.com/docview/1753458928 https://pubmed.ncbi.nlm.nih.gov/PMC3893110 |
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