Clinicopathologic correlates of loss of heterozygosity in Wilms' tumor: A preliminary analysis

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Abstract
Wilms' tumor-specific loss of heterozygosity (LOH) for DNA markers located at chromosomes 11p13, 11p15, 16q, and 1p has been reported to occur in a minority of Wilms' tumors. We hypothesized that tumors classified by region of LOH would exhibit specific clinicopathologic patterns. We have therefore determined the constitutional and tumor genotypes for markers at 11p13, 11p15, 16q, and 1p in a large series of Wilms' tumor patients who were registered on a Pediatric Oncology Group study and on the National Wilms' Tumor Study, to determine whether tumor-specific LOH for any of these regions was associated with any specific phenotype. Of 286 cases, 27% had LOH at both 11p13 and p15 (BOTH), 3% at 11p13 only, 8% at 11p15 only, and 62% at neither. Significant associations were found between younger age at diagnosis and LOH for BOTH, but not for 11p15 only, and between the presence of intralobar nephrogenic rests and LOH for BOTH. The incidence of nephrogenic rests (all types combined) and of bilateral tumors was the same in tumors with or without LOH. There was a negative association between anaplastic histology and LOH for 11p. There was no association between LOH on 11p and outcome as assessed by relapse-free and overall survival. The associations between age at diagnosis and LOH are interpreted as suggesting the existence of a Wilms' tumor locus on 11p in addition to WT1 at 11p13 and the putative WT2 at 11p15. LOH for chromosome 16q was identified in 17% of 204 tumors and was associated with a significantly worse outcome. Outcome for patients with LOH for 1p was also worse but not significantly so.