Kanno H, Kondo K, Ito S, Yamamoto I, Fujii S, Torigoe S, Sakai N, Hosaka M, Shuin T, Yao M
Department of Neurosurgery, Yokohama City University School of Medicine, Japan.
Cancer Res. 1994 Sep 15;54(18):4845-7.
Hemangioblastoma is one of the benign tumors in the central nervous system. It is often associated with the von Hippel-Lindau (VHL) disease, a well known hereditary tumor syndrome. It is believed that inactivation of both alleles of VHL tumor suppressor gene is essential in the tumorigenic processes in hemangioblastomas associated with VHL disease. The molecular basis for the development of sporadic hemangioblastomas is not known. Here, we analyzed 13 cases of primary sporadic hemangioblastomas for somatic mutations of VHL gene with single strand conformational polymorphism analyses of the tumor DNAs. We detected abnormal single strand conformational polymorphism pattern in 7 tumors (54%). Of these 7 possibly mutated tumors, we successfully characterized 3 tumors by direct sequencing. We were unable to sequence 4 tumors because of the poor quality of DNA obtained from paraffin blocks. Somatic mutations in the 3 tumors were 2 missense mutations and 1 microdeletion. These mutations were observed in 1 tumor in exon 1 and 2 tumors in exon 2. Our results suggest that mutations of VHL tumor suppressor gene are involved in the development of at least 20% of sporadic central nervous system hemangioblastomas.
血管母细胞瘤是中枢神经系统的良性肿瘤之一。它常与冯·希佩尔-林道（VHL）病相关，这是一种著名的遗传性肿瘤综合征。据信，VHL肿瘤抑制基因的两个等位基因失活在与VHL病相关的血管母细胞瘤的致瘤过程中至关重要。散发性血管母细胞瘤发生发展的分子基础尚不清楚。在此，我们通过对肿瘤DNA进行单链构象多态性分析，研究了13例原发性散发性血管母细胞瘤中VHL基因的体细胞突变情况。我们在7例肿瘤（54%）中检测到异常的单链构象多态性模式。在这7例可能发生突变的肿瘤中，我们通过直接测序成功鉴定了3例肿瘤。由于从石蜡块中获取的DNA质量较差，我们无法对4例肿瘤进行测序。3例肿瘤中的体细胞突变包括2个错义突变和1个微缺失。这些突变分别出现在1例肿瘤的外显子1和2例肿瘤的外显子2中。我们的结果表明，VHL肿瘤抑制基因的突变至少参与了20%的散发性中枢神经系统血管母细胞瘤的发生发展。
