More than 2% of the adult population of the US harbors a pancreatic cyst and the increasing use of abdominal imaging is likely to increase the diagnosis of these lesions as incidental findings. Because these cysts can either be self-limiting lesions or represent true precursors to deadly invasive adenocarcinomas, they pose a difficult clinical management problem. There are three main forms of pancreatic cystic neoplasms, serous cystic adenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs). SCAs are thought to be totally benign whereas IPMNs and MCNs are often associated with an invasive component. The ultimate goal of this proposal is to develop clinically useful biomarkers that can distinguish these cyst types and alter clinical decision-making. This goal is practical now due to previous successes of this SPORE in the areas of genomic analysis, biomarker development and pancreatic cyst analysis. To achieve this goal, we propose a detailed molecular-analysis of neoplastic cells from all three main types of pancreatic cyst neoplasms (Aim #1). These molecular findings will be used to develop cyst fluid biomarkers (Aim #2). Cyst fluid was chosen as the target clinical sample because of promising preliminary results and because cyst fluid is routinely available in the clinic at critical decision points. The best biomarkers developed in Aim #2 will be correlated with clinical findings and outcomes in both a retrospective (Aim #3) and prospective (Aim #4) manner. The above studies will identify molecular changes that underlie the pathogenesis of pancreatic cyst development and should allow the development of clinically useful cyst fluid biomarkers.

Public Health Relevance

Pancreatic cysts are relatively common and certain types can be precursors to deadly adenocarcinoma of the pancreas. Because of the risk of morbidity and death associated with either the under or over treatment of pancreatic cysts, better diagnostic methods for distinguishing pancreatic cyst type would be highly useful. The goal of this proposal is to develop molecular markers to improve the diagnosis of pancreatic cyst.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA062924-20
Application #
8559516
Study Section
Special Emphasis Panel (ZCA1-RPRB-M)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
20
Fiscal Year
2013
Total Cost
$306,272
Indirect Cost
$116,768
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Adler, B L; Pezhouh, M K; Kim, A et al. (2018) Histopathological and immunophenotypic features of ipilimumab-associated colitis compared to ulcerative colitis. J Intern Med 283:568-577
Ma, Qianqian; Gabelli, Sandra B; Raben, Daniel M (2018) Diacylglycerol kinases: Relationship to other lipid kinases. Adv Biol Regul :
Robinson, Cemre; Estrada, Andrea; Zaheer, Atif et al. (2018) Clinical and Radiographic Gastrointestinal Abnormalities in McCune-Albright Syndrome. J Clin Endocrinol Metab 103:4293-4303
Klein, Alison P; Wolpin, Brian M; Risch, Harvey A et al. (2018) Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer. Nat Commun 9:556
Kuboki, Yuko; Fischer, Catherine G; Beleva Guthrie, Violeta et al. (2018) Single-cell sequencing defines genetic heterogeneity in pancreatic cancer precursor lesions. J Pathol :
Zhang, Jiajia; Quadri, Shafat; Wolfgang, Christopher L et al. (2018) New Development of Biomarkers for Gastrointestinal Cancers: From Neoplastic Cells to Tumor Microenvironment. Biomedicines 6:
Hata, Tatsuo; Suenaga, Masaya; Marchionni, Luigi et al. (2018) Genome-Wide Somatic Copy Number Alterations and Mutations in High-Grade Pancreatic Intraepithelial Neoplasia. Am J Pathol 188:1723-1733
Noë, Michaël; Rezaee, Neda; Asrani, Kaushal et al. (2018) Immunolabeling of Cleared Human Pancreata Provides Insights into Three-Dimensional Pancreatic Anatomy and Pathology. Am J Pathol 188:1530-1535
Schunke, Kathryn J; Rosati, Lauren M; Zahurak, Marianna et al. (2018) Long-term analysis of 2 prospective studies that incorporate mitomycin C into an adjuvant chemoradiation regimen for pancreatic and periampullary cancers. Adv Radiat Oncol 3:42-51
Zhang, Jiajia; Wolfgang, Christopher L; Zheng, Lei (2018) Precision Immuno-Oncology: Prospects of Individualized Immunotherapy for Pancreatic Cancer. Cancers (Basel) 10:

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