We have prospectively analyzed Wilms' tumors from 232 patients registered 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, respectively. LOH for two of these regions occurred in only 25 cases, and only one tumor harbored LOH at all three sites. There was no statistically significant association between LOH at any of the three regions and either the stage or histological classification of the tumor. Patients with tumorspecific 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 remained when adjusted for histology or for stage. Patients with LOH for chromosome 1p had relapse and mortality rates three times higher than those for patients without LOH for chromosome 1p, but these results were not statistically significant. In contrast, LOH for chromosome 11p had 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 trial mechanism in the study of Wilms' tumor.

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Wilms' tumors and patient DNA were obtained through the mechanism of protocol 9046 of the POG (Chicago, IL), which is supported by the National Cancer Institute. Clinical data was obtained through the National Wilms' Tumor Study supported by USPHS Grant CA-42326. This work was supported in part by the National Cancer Institute and the Medical Research Council of Canada, the Children's Health Foundation of Northern Alberta, the Cancer Research Society, and by Grant CA60114-01 from the National Cancer Institute of the NIH. P. G. is a Clinical Investigator, and M. C. P. is a Medical Scientist of the Alberta Heritage Foundation for Medical Research.

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