Familial predisposition to Wilms' tumour does not map to the short arm of chromosome 11

Abstract

Wilms⁹ tumour of the kidney usually occurs sporadically, but can also segregate as an autosomal dominant trait with incomplete penetrance^{1, 2}. Patients with the WAGR syndrome of aniridia, genitourinary anomalies, mental retardation and high risk of Wilms' tumour have overlapping deletions of chromosome Hpl3 (ref. 3) which has suggested a possible location for a Wilms' tumour locus. Moreover, many sporadic tumours have lost a portion of chromosome lip (refs ^4–8). A second locus at llplS is implicated by association of the tumour with the Wiedemann-Beckwith syndrome (refs ^9–11) and by tumour-specific losses of chromosome 11 confined to lip 15 (ref. 12). Here we report a multipoint linkage analysis of a family segregating for Wilms' tumour, using polymorphic DNA markers mapped to chromosome lip. 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^{13, 14}.