Abstract
BACKGROUND: Wilms tumor (WT) is the most common childhood kidney cancer worldwide and arises in children of black African ancestry with greater frequency and severity than other race groups. A biologic basis for this pediatric cancer disparity has not been previously determined. We hypothesized that unique molecular fingerprints might underlie the variable incidence and distinct disease characteristics of WT observed between race groups. STUDY DESIGN: To evaluate molecular disparities between WTs of different race groups, the Children's Oncology Group provided 80 favorable histology specimens divided evenly between black and white patients and matched for disease characteristics. As a surrogate of black sub-Saharan African patients, we also analyzed 18 Kenyan WT specimens. Tissues were probed for peptide profiles using matrix-assisted laser desorption ionization time of flight imaging mass spectrometry. To control for histologic variability within and between specimens, cellular regions were analyzed separately as triphasic (containing blastema, epithelia, and stroma), blastema only, and stroma only. Data were queried using ClinProTools and statistically analyzed. RESULTS: Peptide profiles, detected in triphasic WT regions, recognized race with good accuracy, which increased for blastema- or stroma-only regions. Peptide profiles from North American WTs differed between black and white race groups but were far more similar in composition than Kenyan specimens. Individual peptides were identified that also associated with WT patient and disease characteristics (eg, treatment failure and stage). Statistically significant peptide fragments were used to sequence proteins, revealing specific cellular signaling pathways and candidate drug targets. CONCLUSIONS: Wilms tumor specimens arising among different race groups show unique molecular fingerprints that could explain disparate incidences and biologic behavior and that could reveal novel therapeutic targets.