Loss of Heterozygosity for Chromosomes 16q and ip in Wilms' Tumors Predicts an Adverse Outcome

We have prospectivelyanalyzed Wilms' tumors from 232 patients registered on the National Wilms' Tumor Study for loss of heterozygosity (LOll) on chromosomes lip, 16q, and ip. These chromosomal aberrations werefoundin 70(33%),35 (17%),and 21 (12%)ofthe informativecases, respectively. LOH for two of these regions occurred in only 25 cases, and only one tumor harboredLOll at all three sites Therewas no statistically significantassociationbetweenLOHat anyofthe three regionsand either the stage or histologicalclassificationof the tumor. Patients with tumor specificLOHfor chromosome16q had relapserates3.3 times higher(P = 0.01) andmortality rates 12times higher (P<0.01) than patients without LOH for chromosome i6q. These differences remained when adjusted for histology or for stage. Patients with LOH for chromosome ip had relapse and mortality rates three times higher than those for patients without LOH for chromosome ip, but these results were not statistically signifi cant. In contrast, LOH for chromosome lip 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 Wilma' tumor.