Loss of a Harvey ras allele in sporadic Wilms' tumour

Abstract
Genomic changes within chromosome band 11p13 appear to have a role in the initiation of Wilms' tumour1–7. The human Harvey ras oncogene, c-Ha-ras1, has been located by Jhanwar et al.8 immediately adjacent to this region at band 11p14.1, although several groups have assigned the gene more distally at band 11p15 (refs 9–11). We have examined tumour DNA from two cases of sporadic Wilms' tumour, and report here that in both cases one of the two constitutional c-Ha-ras1 alleles was absent. One tumour had a reciprocal translocation between the short arm of chromosome 11 (at band 11p13), and the long arm of chromosome 12, with no visible loss of chromosomal material. The loss of a c-Ha-ras1 allele in association with this translocation indicates that a submicroscopic deletion had occurred. The resulting hemizygosity may have had a role in tumour initiation. Our results indicate that the c-Ha-ras1 gene and the ‘Wilms' tumour locus’ may be in close proximity. It would, therefore, be premature to exclude the possibility that these two sites are functionally related.