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

R Vuononvirta, NJ Sebire, AR Dallosso, JS Reis-Filho, RD Williams, A Mackay, K Fenwick, A Grigoriadis, A Ashworth, K Pritchard-Jones, KW Brown, G Vujanic, C Jones

Research output: Contribution to journalArticle (Academic Journal)peer-review

22 Citations (Scopus)

Abstract

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.
Translated title of the contributionPerilobar nephrogenic rests are nonobligate molecular genetic precursor lesions of insulin-like growth factor-II-associated Wilms tumors
Original languageEnglish
Pages (from-to)7635 - 7644
Number of pages10
JournalClinical Cancer Research
Volume14
DOIs
Publication statusPublished - Dec 2008

Bibliographical note

Publisher: American Association for Cancer Research

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