LAUSR

Simple Summary We reviewed all studies investigating molecular changes in nephrogenic rests (NR), the presumed precursor lesions of Wilms tumors (WT) being the most frequent malignant childhood renal tumors, between 1990 and 2022. Only 23 studies were found, reporting 119 pairs of NR and corresponding WT, which may allow the detection of early genetic changes that play a role in tumorigenesis. Two genes, WT1 and WTX, and two chromosomal regions, 11p13 where WT1 is located, and 11p15 harboring the IGF-2 gene, were found to be mutated or show loss of imprinting, respectively, in both nephrogenic rests and WT, suggesting that these could be relevant early genetic events. Abstract Objective: To review somatic genetic changes in nephrogenic rests (NR), which are considered to be precursor lesions of Wilms tumors (WT). Methods: This systematic review is written according to the PRISMA statement. PubMed and EMBASE were systematically searched for articles in the English language studying somatic genetic changes in NR between 1990 and 2022. Results: Twenty-three studies were included in this review, describing 221 NR of which 119 were pairs of NR and WT. Single gene studies showed mutations in WT1 and WTX, but not CTNNB1 to occur in both NR and WT. Studies investigating chromosomal changes showed loss of heterozygosity of 11p13 and 11p15 to occur in both NR and WT, but loss of 7p and 16q occurred in WT only. Methylome-based studies found differential methylation patterns between NR, WT, and normal kidney (NK). Conclusions: Over a 30-year time frame, few studies have addressed genetic changes in NR, likely hampered by technical and practical limitations. A limited number of genes and chromosomal regions have been implicated in the early pathogenesis of WT, exemplified by their occurrence in NR, including WT1, WTX, and genes located at 11p15. Further studies of NR and corresponding WT are urgently needed.