Serum Markers /Angiogenesis in von Hippel-Lindau Disease

描述(由申请人提供)： Von Hippei-Lindau病(VHL)是一种罕见的常染色体显性遗传性肿瘤易感综合征，其特征是多系统的良、恶性肿瘤，以血管新生增殖为特征。患者的平均年龄为26岁；25%-43%的患者患有视网膜血管母细胞瘤，而35%-39%的患者患有小脑血管母细胞瘤。然而，患者在生命的第一个十年可能会有症状；因此，未来临床前干预的尝试可能会针对儿科和成人人群。 在这一应用中，我们采取了初步步骤来开发新视疲劳的临床前标记物。我们将建立一个血清库和冯·希佩尔-林道病家庭登记。我们推测，在基因确定为VHL的患者中，血清中的血管内皮生长因子及其可溶性受体sVEGFR1的水平可能与突变阴性的对照组有显著不同。我们将分析突变阳性和年龄匹配的突变阴性个体的血清中血管内皮生长因子和可溶性血管内皮生长因子-R1的水平。 我们将确定VHL疾病的严重程度与血清中血管内皮生长因子及其受体水平的相关性。我们将根据突变亚型分析血清水平。随着更多的血管生成标志物变得已知，我们将处于战略地位，可以对从这些高危个体那里储存的血清样本进行分析。 在德克萨斯州北部建立VHL登记也将使我们处于一个极好的地位，以开发旨在早期发现VHL患者损害的临床方案。

DESCRIPTION (provided by applicant): Von HippeI-Lindau disease (VHL) is a rare autosomal dominant tumor predisposition syndrome characterized by multi-system benign and malignant tumors characterized by angiogenic proliferation. Patients present at an average age of 26 years; 25-43 percent present with retinal hemangioblastoma, while 35-39 percent present with cerebellar hemangioblastoma. However, patients may be symptomatic during the first decade of life; therefore, future attempts at pre-clinical intervention will likely target both pediatric and adult populations. In this application, we take the initial steps to develop pre-clinical markers of neoptasia. We will establish a serum bank and a registry of families with Von Hippel-Lindau Disease. We hypothesize that serum levels of VEGF and its soluble receptor sVEGFR1 may be significantly different in patients genetically determined to have VHL than in mutation-negative controls. We will analyze serum from mutation-positive and age matched mutation negative individuals for levels of VEGF and sVEGF-R1. We will determine the correlation between severity of VHL disease and the serum levels of VEGF and sVEGF-R1. We will analyze serum levels in terms of mutation sub-type. As additional markers of angiogenesis become known, we will be strategically placed to perform analyses on our serum samples banked from these high-risk individuals. The establishment of a VHL registry in North Texas will also place us in an excellent position to develop clinical protocols aimed towards early detection of lesions in VHL patients.