Duffy Karen, Al-Saleem Tahseen, Karbowniczek Magdalena, Ewalt David, Prowse Amanda H, Henske Elizabeth Petri
Medical Oncology Division, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Mod Pathol. 2002 Mar;15(3):205-10. doi: 10.1038/modpathol.3880517.
Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by seizures, mental retardation, autism, and tumors of multiple organs. Renal disease in TSC includes angiomyolipomas, cysts, and renal cell carcinomas. It is known that somatic mutations in the von Hippel Lindau (VHL) tumor suppressor gene occur in most clear cell renal carcinomas. To determine whether TSC-associated clear cell carcinomas also contain VHL mutations, we analyzed six tumors for loss of heterozygosity in the VHL gene region of chromosome 3p and for mutations in the VHL gene. Four of the patients were women between the ages of 34 and 68 years, and two were males under the age of 21 years. The loss of heterozygosity analysis was performed using polymorphic microsatellite markers, and the mutational analysis was performed using direct sequencing. Chromosome 3p loss of heterozygosity was not detected, and no VHL mutations were identified. These findings suggest that mutations in the TSC1 and TSC2 genes lead to clear cell renal carcinogenesis via an alternate pathway not involving VHL mutations.
结节性硬化症（TSC）是一种常染色体显性疾病，其特征为癫痫发作、智力迟钝、自闭症以及多器官肿瘤。TSC相关的肾脏疾病包括血管平滑肌脂肪瘤、囊肿和肾细胞癌。已知在大多数透明细胞肾细胞癌中会发生von Hippel Lindau（VHL）肿瘤抑制基因的体细胞突变。为了确定TSC相关的透明细胞癌是否也含有VHL突变，我们分析了6个肿瘤，检测其3号染色体p区域VHL基因区域的杂合性缺失以及VHL基因的突变情况。其中4名患者为年龄在34至68岁之间的女性，2名患者为21岁以下的男性。使用多态性微卫星标记进行杂合性缺失分析，使用直接测序进行突变分析。未检测到3号染色体p区域的杂合性缺失，也未发现VHL突变。这些发现表明，TSC1和TSC2基因的突变通过不涉及VHL突变的替代途径导致透明细胞肾癌的发生。
