Decker H J, Weidt E J, Brieger J
Department of Hematology and Oncology, Johannes-Gutenberg University, Mainz, Germany.
Cancer Genet Cytogenet. 1997 Jan;93(1):74-83. doi: 10.1016/s0165-4608(96)00296-8.
The von Hippel-Lindau (VHL) disease is an inherited tumor susceptibility syndrome featuring a high variety of benign and malignant tumors. The gene has been localized and cloned at 3p25-26. Recent functional analysis defined the VHL gene product as an inhibitor of the transcription elongation process. Its possible involvement in the vascularization process may explain the histologic features of VHL tumors providing insight into basic mechanism of tumorigenesis. Direct genetic testing is available for patients affected with VHL. Seventy to eighty percent of the germline mutations expected could be detected. As first geno/phenotype correlations have been established, we are now beginning to understand the diversity of this fascinating disease at the molecular level. As mutational analysis proved to be of striking prognostic significance, gene testing became an important tool for the management of the disease. The VHL gene was also found to be responsible for tumorigenesis in the corresponding sporadic tumors, especially in the clear cell type of renal cell carcinomas. The understanding of the normal and disturbed function of the VHL gene product will enable us to develop treatment strategies based on and targeted at the molecular cause of the disease. In this review we summarize the current knowledge about genetics, clinics, and function of VHL.
冯·希佩尔-林道（VHL）病是一种遗传性肿瘤易感性综合征，其特征是有多种良性和恶性肿瘤。该基因已被定位并克隆于3p25 - 26。最近的功能分析将VHL基因产物定义为转录延伸过程的抑制剂。它可能参与血管生成过程，这可以解释VHL肿瘤的组织学特征，从而深入了解肿瘤发生的基本机制。对于受VHL影响的患者可进行直接基因检测。预期可检测到70%至80%的种系突变。由于已经建立了最初的基因型/表型相关性，我们现在开始在分子水平上理解这种迷人疾病的多样性。由于突变分析被证明具有显著的预后意义，基因检测成为该疾病管理的重要工具。还发现VHL基因与相应散发性肿瘤的肿瘤发生有关，特别是在透明细胞型肾细胞癌中。对VHL基因产物正常和紊乱功能的理解将使我们能够基于该疾病的分子病因并针对其开发治疗策略。在本综述中，我们总结了关于VHL的遗传学、临床和功能的当前知识。
