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Pancreatic cyst development: insights from von Hippel-Lindau disease

Sophie J van Asselt12, Elisabeth GE de Vries2, Hendrik M van Dullemen3, Adrienne H Brouwers4, Annemiek ME Walenkamp2, Rachel H Giles5 and Thera P Links1*

Author Affiliations

1 Department of Endocrinology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands

2 Department of Medical Oncology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands

3 Department of Gastroenterology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands

4 Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands

5 Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands

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Cilia 2013, 2:3  doi:10.1186/2046-2530-2-3

Published: 5 February 2013

Abstract

Pancreatic cysts are a heterogeneous group of lesions, which can be benign or malignant. Due to improved imaging techniques, physicians are more often confronted with pancreatic cysts. Little is known about the origin of pancreatic cysts in general. Von Hippel-Lindau (VHL) disease is an atypical ciliopathy and inherited tumor syndrome, caused by a mutation in the VHL tumor suppressor gene encoding the VHL protein (pVHL). VHL patients are prone to develop cysts and neuroendocrine tumors in the pancreas in addition to several other benign and malignant neoplasms. Remarkably, pancreatic cysts occur in approximately 70% of VHL patients, making it the only hereditary tumor syndrome with such a discernible expression of pancreatic cysts. Cellular loss of pVHL due to biallelic mutation can model pancreatic cystogenesis in other organisms, suggesting a causal relationship. Here, we give a comprehensive overview of various pVHL functions, focusing on those that can potentially explain pancreatic cyst development in VHL disease. Based on preclinical studies, cilia loss in ductal cells is probably an important early event in pancreatic cyst development.

Keywords:
Cilia; Cytoskeleton; Pancreatic cysts or serous cystadenomas; VHL tumor suppressor protein; von Hippel-Lindau disease