Uniparental disomy occurs infrequently in Wilms tumor patients.

Wilms tumors commonly exhibit loss of heterozygosity for polymorphic DNA markers located on the short arm of chromosome 11 at band p15. In some instances, the deleted region does not include 11p13, the location of the WT1 gene, suggesting the existence of a second Wilms tumor gene on 11p. Both the exclusive loss of the maternally derived allele in Wilms tumors and the recent description of constitutional paternal isodisomy for this region in patients with either the Beckwith-Wiedemann syndrome (BWS) or isolated hemihypertrophy have suggested that this second locus is subject to sex-specific genomic imprinting. Given that one of these isodisomic patients had minimal congenital anomalies (hemihypertrophy), we hypothesized that a proportion of Wilms tumors which had not lost heterozygosity for 11p markers (about 60% of all cases) might have arisen consequent to 11p paternal heterodisomy and that patients constitutionally homozygous at 11p15 might harbor paternal isodisomy. We have analyzed 40 Wilms tumor cases to determine the parental origin of the child's 11p15 alleles. Paternal heterodisomy could be excluded in all 28 unilateral and 8/9 bilateral potential candidates. It is intriguing that somatic mosaicism for 11p paternal isodisomy was detected in one child with bilateral Wilms tumor and macroglossia. Isodisomy could only be excluded in one of the three possible cases. Thus, 11p paternal hetero- and isodisomy appear to be uncommon causes of non-anomaly-associated Wilms tumors but may be more frequent in Wilms tumor patients with BWS-associated anomalies.