Perilobar nephrogenic rests are nonobligate molecular genetic precursor lesions of insulin-like growth factor-II-associated Wilms tumors

Purpose: Perilobar nephrogenic rests (PLNRs) are abnormally persistent foci of embryonal immature blastema that have been associatedw ith dysregulation at the 11p15 locus by genetic/ epigenetic means anda re thought to be precursor lesions ofWilms tumor. The precise genomic events are, however, largely unknown. Experimental Design:We usedar ray comparative genomic hybridization to analyze a series of 50 PLNRs and2 5 correspondingWilms tumors characterized for 11p15 genetic/epigenetic alterations andi nsulin-like growth factor-II expression. Results:The genomic profiles of PLNRs couldbe subdividedinto three categories: thosewith no copy number changes (22 of 50, 44%); those with single, whole chromosome alterations (8 of 50, 16%); andt hose with multiple gains/losses (20 of 50, 40%). The most frequent aberrations included1p- (7 of 50,14%) +18 (6 of 50,12%), +13 (5 of 50,10%), and +12 (3 of 50, 6%). For the majority (19 of 25, 76%) of cases, the rest harboreda subset of the copy number changes in the associatedWilms tumor.We identified a temporal order of genomic changes, which occur during the insulin-like growth factor-II/PLNR pathway ofWilms tumorigenesis,with large-scale chromosomal alterations such as1p-, +12, +13, and+18 regarded as ‘‘early’’events. In some of the cases (24%), the PLNRs harboredl arge-scale copy number changes not observed in the concurrent Wilms tumor, including +10p, +14q, and +18. Conclusions: These data suggest that although the evidence for PLNRs as precursors is compelling, not all lesions must necessarily undergo malignant transformation.