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

Clin Cancer Res. 2008 Dec 1;14(23):7635-44. doi: 10.1158/1078-0432.CCR-08-1620.


Purpose: Perilobar nephrogenic rests (PLNRs) are abnormally persistent foci of embryonal immature blastema that have been associated with dysregulation at the 11p15 locus by genetic/epigenetic means and are thought to be precursor lesions of Wilms tumor. The precise genomic events are, however, largely unknown.

Experimental design: We used array comparative genomic hybridization to analyze a series of 50 PLNRs and 25 corresponding Wilms tumors characterized for 11p15 genetic/epigenetic alterations and insulin-like growth factor-II expression.

Results: The genomic profiles of PLNRs could be subdivided into three categories: those with no copy number changes (22 of 50, 44%); those with single, whole chromosome alterations (8 of 50, 16%); and those with multiple gains/losses (20 of 50, 40%). The most frequent aberrations included 1p- (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 harbored a subset of the copy number changes in the associated Wilms tumor. We identified a temporal order of genomic changes, which occur during the insulin-like growth factor-II/PLNR pathway of Wilms tumorigenesis, with large-scale chromosomal alterations such as 1p-, +12, +13, and +18 regarded as "early" events. In some of the cases (24%), the PLNRs harbored large-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Comparative Genomic Hybridization
  • DNA Methylation
  • Gene Dosage
  • Humans
  • Insulin-Like Growth Factor II / metabolism*
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Loss of Heterozygosity
  • Molecular Sequence Data
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Wilms Tumor / genetics*
  • Wilms Tumor / metabolism


  • IGF2 protein, human
  • Insulin-Like Growth Factor II