Moutou C, Chompret A, Hochez J, Tournade M F, Zucker J M, Lemerle J, Junien C, Bonaïti-Pellié C
Unité de Recherches d'Epidémiologie Génétique, (INSERM U-155), Paris, France.
Eur J Hum Genet. 1993;1(3):190-205. doi: 10.1159/000472413.
Data from 511 cases of Wilms' tumor in France (including 12 familial cases) and 8 pedigrees from the literature were analyzed to test three modifications of Knudson's classical bimutational theory, based on genomic imprinting in Wilms' tumor carcinogenesis. Analysis of data of age at diagnosis and segregation analysis were performed to determine the number of independent events for Wilms' tumor development and to search for a differential role of paternal and maternal alleles. Unexpectedly, we show that only one rare event is required for tumor development in isolated unilateral cases which are considered to be mainly nonhereditary. In familial cases, we observe no effect of the sex of the transmitting parent on either hge at diagnosis or segregation ratio. We show that this could be explained by models of genomic imprinting which assume two nonindependent events, or only one rare genetic event. In bilateral cases we show a bimodality for age at diagnosis which could be due to a mixture of hereditary and nonhereditary cases. This result completely questions the classical assumption according to which all bilateral cases would be hereditary. These findings support the hypothesis that this childhood cancer arises from a variety of etiological pathways and might be useful to find strategies for further molecular investigations.
分析了来自法国的511例肾母细胞瘤病例（包括12例家族性病例）以及文献中的8个家系的数据，以检验基于肾母细胞瘤致癌过程中基因组印记的Knudson经典双突变理论的三种修正。进行了诊断年龄数据分析和分离分析，以确定肾母细胞瘤发生所需的独立事件数量，并寻找父本和母本等位基因的差异作用。出乎意料的是，我们发现，在被认为主要是非遗传性的孤立单侧病例中，肿瘤发生仅需要一个罕见事件。在家族性病例中，我们观察到传递亲本的性别对诊断年龄或分离比均无影响。我们表明，这可以通过假设两个非独立事件或仅一个罕见遗传事件的基因组印记模型来解释。在双侧病例中，我们发现诊断年龄呈双峰分布，这可能是由于遗传性和非遗传性病例的混合所致。这一结果完全质疑了所有双侧病例均为遗传性的经典假设。这些发现支持了这样的假设，即这种儿童癌症源于多种病因途径，可能有助于找到进一步分子研究的策略。
