LOSS OF HETEROZYGOSITY FOR CHROMOSOMES 16Q AND 1P IN WILMS-TUMORS PREDICTS AN ADVERSE OUTCOME

We have prospectively analyzed Wilms' tumors from 232 patients registe red on the National Wilms' Tumor Study for loss of heterozygosity (LOH ) on chromosomes 11p, 16q, and 1p. These chromosomal aberrations were found in 70 (33%), 35 (17%), and 21 (12%) of the informative cases, re spectively. LOH for two of these regions occurred in only 25 cases, an d only one tumor harbored LOH at all three sites. There was no statist ically significant association between LOH at any of the three regions and either the stage or histological classification of the tumor. Pat ients with tumor-specific LOH for chromosome 16q had relapse rates 3.3 times higher (P = 0.01) and mortality rates 12 times higher (P < 0.01 ) than patients without LOH for chromosome 16q. These differences rema ined when adjusted for histology or for stage. Patients with LOH for c hromosome 1p had relapse and mortality rates three times higher than t hose for patients without LOH for chromosome 1p, but these results wer e not statistically significant. In contrast, LOH for chromosome 11p h ad no effect on measures of outcome. These molecular markers may serve to further stratify Wilms' tumor patients into biologically favorable and unfavorable subgroups, allowing continued use of the clinical tri al mechanism in the study of Wilms' tumor.