Mentor Name: Jennifer Kalish

This research project investigates the occurrence and evolution of nephrogenic rests in patients with Beckwith-Wiedemann syndrome (BWS). Nephrogenic rests are embryonal kidney tissue that develop in a subset of patients with BWS. While nephrogenic rests can remain benign, some undergo malignant transformation into Wilms tumor, an embryonal renal tumor of which patients with BWS have a markedly elevated predisposition. The thorough investigation of nephrogenic rests in BWS may enable an enhanced understanding of the potential factors that predict progression to Wilms tumor and is vital for optimizing surveillance and clinical management. The project will involve a comprehensive literature review of nephrogenic rests to assess the existing limited literature on this topic and an investigation of our BWS cohort. Specific study objectives include determining the incidence of nephrogenic rests across BWS molecular subtypes, analyzing the average age of development, examining correlations with degrees of blood mosaicism and phenotypic burden, and quantifying the rate of malignant transformation to Wilms tumor. Data from pathology reports of patients who have undergone resection of nephrogenic rest will be reviewed. Additionally, the natural history and severity of disease of Wilms tumor in patients with or without previous nephrogenic rest developed will be assessed. And lastly, the timing and efficacy of imaging modalities for diagnosis and treatment interventions in use at our institution will be assessed. Data acquisition and comprehensive chart review will be conducted from the BWS Registry using the EPIC electronic health record system. Data will be organized and stored in Microsoft Excel, with statistical analysis performed using R-Studio. Data findings will be reviewed with geneticists and oncologists, and the discussion will guide whether there are additional data points or investigations to be performed. Ultimately, the findings from this project will be synthesized into a manuscript which will translate results in a manner than can inform clinical care and screening for this high-risk population.