Race Disparities in Genomic Alterations Within Wilms Tumor Specimens

Background/Purpose: Wilms tumor (WT) affects black children of sub-Saharan ancestry disproportionately. Genetic aberrations that drive this cancer health disparity have not been reported.

Methods: The Children’s Oncology Group TARGET database was queried for WT patient characteristics and genomic analyses. Clinical and genomic variables were compared between patients registered as black or white. Appropriate statistical tests were applied to compare continuous and categorical variables.

Results (Table): Within the TARGET discovery set (enriched for adverse events; N = 94 white, 19 black, 14 other/unreported patients), no differences in clinical features or outcomes were detected. Within the TARGET validation set (random, one-third sampling of NWTS-5; N = 360 white, 92 black, 72 other/unreported patients), black children appeared older at diagnosis (p=0.050) and over-represented (17.6%) relative to the 2010 US Census (13.4%). When combining both data sets, 22 (19.8%) black and 78 (17.2%) white patients were deceased (p=0.514). Five-year overall survival was 76.9% for black patients and 82.7% for white patients (p=0.348). Median follow-up was less for black (6.0 years) than white patients (10.0 years; p<0.000). Within the discovery set, no differences between black and white specimens for copy number gain at 1q and amplification at 2p24 (MYCN) were observed. Among all patients, white children were more likely to have one or multiple targeted genetic mutations compared to black children (p=0.026). Mutations in ACTB (p=0.030) and DICER1 (p=0.026) were more common in black patient specimens, whereas DGCR8 (p=0.041) mutations were more common among white patient specimens.

Conclusion: Black children were older at WT diagnosis and harbored specimens containing more frequent ACTB and DICER1 mutations. WT specimens of white patients more commonly contained multiple mutations in the 37 TARGET genes and in DGCR8. Genetic alterations in WT specimens unique to race may inform mechanisms contributing to disparate Wilms tumorigenesis and reveal targets for personalized therapy.