van Asselt Sophie J, de Vries Elisabeth Ge, van Dullemen Hendrik M, Brouwers Adrienne H, Walenkamp Annemiek Me, Giles Rachel H, Links Thera P
Department of Endocrinology, University of Groningen, University Medical Center Groningen, PO Box 30,001, 9700 RB, Groningen, The Netherlands.
Cilia. 2013 Feb 5;2(1):3. doi: 10.1186/2046-2530-2-3.
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.
胰腺囊肿是一组异质性病变，可为良性或恶性。由于成像技术的改进，医生更常遇到胰腺囊肿。总体而言，人们对胰腺囊肿的起源知之甚少。冯·希佩尔-林道（VHL）病是一种非典型纤毛病和遗传性肿瘤综合征，由编码VHL蛋白（pVHL）的VHL肿瘤抑制基因突变引起。除了其他几种良性和恶性肿瘤外，VHL患者还容易在胰腺中发生囊肿和神经内分泌肿瘤。值得注意的是，约70%的VHL患者会出现胰腺囊肿，这使其成为唯一具有如此明显胰腺囊肿表现的遗传性肿瘤综合征。由于双等位基因突变导致的pVHL细胞缺失可在其他生物体中模拟胰腺囊肿发生，提示存在因果关系。在此，我们全面概述了各种pVHL功能，重点关注那些可能解释VHL病中胰腺囊肿发展的功能。基于临床前研究，导管细胞中的纤毛缺失可能是胰腺囊肿发展中的一个重要早期事件。
