BIOLOGICAL PROGNOSTIC FACTORS IN WILMS TUMOR

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DESCRIPTION (Applicant's Description): The survival rate for children with Wilms tumor has improved dramatically. The projected five-year survival rate for children 0-14 years of age with Wilms tumor is 91.7 percent, a statistically significant improvement when compared to that for the period 1974-1976. Treatment in the past was based on tumor extent (stage) and histology. These factors fail to accurately identify the 15 percent of patients who relapse despite modern therapy. We propose to evaluate several new biological markers to determine if they can be utilized for pre-therapy stratification of patients with Wilms tumor into those with a low, and those with a high risk of relapse. The factors we will evaluate are: 1) Loss of heterozygosity at 22q and 7p; 2) Mutation at the GPC3 locus; 3) Telomerase activity in tumor tissue; 4) Aberrant WT1 mRNA splicing; and 5) Loss of heterozygosity at 5q. We will study these potential markers using a case-cohort design. If one or more of these factors is shown to predict relapse, independent of stage and histology, that factor(s) will be investigated in a confirmatory analysis using the patient population accrued to the next National Wilms Tumor Study Group therapeutic trial.