Grundy P, Koufos A, Morgan K, Li F P, Meadows A T, Cavenee W K
Ludwig Institute for Cancer Research, Royal Victoria Hospital, Montreal, Canada.
Nature. 1988 Nov 24;336(6197):374-6. doi: 10.1038/336374a0.
Wilms' tumour of the kidney usually occurs sporadically, but can also segregate as an autosomal dominant trait with incomplete penetrance. Patients with the WAGR syndrome of aniridia, genitourinary anomalies, mental retardation and high risk of Wilms' tumour have overlapping deletions of chromosome 11p13 which has suggested a possible location for a Wilms' tumour locus. Moreover, many sporadic tumours have lost a portion of chromosome 11p. A second locus at 11p15 is implicated by association of the tumour with the Wiedemann-Beckwith syndrome and by tumour-specific losses of chromosome 11 confined to 11p15. Here we report a multipoint linkage analysis of a family segregating for Wilms' tumour, using polymorphic DNA markers mapped to chromosome 11p. The results exclude the predisposing mutation from both locations. In a second family, the 11p15 alleles lost in the tumour were derived from the affected parent, thus precluding this region as the location of the inherited mutation. These findings imply an aetiological heterogeneity for Wilms' tumour and raise questions concerning the general applicability of the carcinogenesis model that has been useful in the understanding of retinoblastoma.
肾母细胞瘤通常为散发性，但也可作为一种显性遗传特征不完全外显的疾病发生分离。患有无虹膜、泌尿生殖系统异常、智力发育迟缓以及肾母细胞瘤高风险的WAGR综合征患者，其11号染色体p13区域存在重叠缺失，这表明肾母细胞瘤基因座可能位于该区域。此外，许多散发性肿瘤也缺失了11号染色体p部分区域。11号染色体p15区域被认为是另一个基因座，依据是该肿瘤与威德曼-贝克威思综合征的关联，以及肿瘤特异性的11号染色体缺失局限于11p15区域。在此，我们报告了一个肾母细胞瘤家族的多点连锁分析，使用定位在11号染色体p区域的多态性DNA标记。结果排除了这两个区域存在致病突变的可能性。在另一个家族中，肿瘤中丢失的11p15等位基因源自患病的父母，因此排除了该区域为遗传突变所在位置。这些发现意味着肾母细胞瘤存在病因异质性，并对在理解视网膜母细胞瘤方面颇为有用的致癌模型的普遍适用性提出了质疑。
