Evidence for clonal development of Wilms' tumor.

To assess the clonality of Wilms' tumor, glucose-6-phosphate dehydrogenase (G6PD) enzymes were studied in normal and tumor tissue from 11 black girls who were heterozygous for G6PD. Normal tissues expressed both A and B type G6PD, whereas only a single G6PD enzyme was found in all tumor specimens. These data support the clonal nature of Wilms' tumor. In the one patient with bilateral disease, type B G6PD was found in both a recurrence and a subsequent tumor in the contralateral kidney. This finding is consistent with either the chance occurrence of the same G6PD in independent tumors or persistence of the original malignant clone. Another patient, who presented with the nephroblastomatosis complex (a precursor of Wilms' tumor), also had only type B enzyme detected. Further studies in patients with bilateral disease or the nephroblastomatosis complex, including the use of molecular biologic probes, are needed to test the hypothesis that Wilms' tumor in these cases arises from a somatic mutation as a second event in persons with an underlying genetic alteration.