Maher E R, Yates J R, Ferguson-Smith M A
Cambridge University Department of Pathology.
J Med Genet. 1990 May;27(5):311-4. doi: 10.1136/jmg.27.5.311.
Analysis of the age incidence curves for unilateral and bilateral retinoblastoma led Knudson to propose that hereditary tumours may arise by a single event and sporadic tumours by a two stage mutation process. It has been suggested recently that sporadic renal cell carcinoma may arise from a two stage mutation process. We analysed the age incidence curves for symptomatic renal cell carcinoma (n = 26) and cerebellar haemangioblastoma (n = 68) in 109 patients with von Hippel-Lindau (VHL) disease, and compared them to 104 patients with sporadic renal cell carcinoma and 43 patients with sporadic cerebellar haemangioblastoma. The age incidence curves for renal cell carcinoma and cerebellar haemangioblastoma in VHL disease were compatible with a single mutation model, whereas the age incidence curves for sporadic renal cell carcinoma and cerebellar haemangioblastoma suggested a two stage mutation process. These data are compatible with the VHL gene functioning as a recessive tumour suppressor gene. Sporadic cerebellar haemangioblastoma and some renal cell carcinoma may arise from somatic mutations inactivating both alleles at the VHL locus.
对单侧和双侧视网膜母细胞瘤的年龄发病率曲线分析使克努森提出，遗传性肿瘤可能由单个事件引发，而散发性肿瘤则通过两阶段突变过程产生。最近有人提出，散发性肾细胞癌可能源于两阶段突变过程。我们分析了109例冯·希佩尔-林道（VHL）病患者中症状性肾细胞癌（n = 26）和小脑成血管细胞瘤（n = 68）的年龄发病率曲线，并将其与104例散发性肾细胞癌患者和43例散发性小脑成血管细胞瘤患者进行比较。VHL病中肾细胞癌和小脑成血管细胞瘤的年龄发病率曲线与单突变模型相符，而散发性肾细胞癌和小脑成血管细胞瘤的年龄发病率曲线提示两阶段突变过程。这些数据与VHL基因作为隐性肿瘤抑制基因发挥作用相符。散发性小脑成血管细胞瘤和一些肾细胞癌可能源于VHL基因座上两个等位基因均失活的体细胞突变。
