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


METHODS
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.
Vuononvirta
Raisa
R
Paediatric Oncology, Institute of Cancer Research/Royal Marsden NHS Trust, Sutton, United Kingdom.
Sebire
Neil J
NJ
Dallosso
Anthony R
AR
Reis-Filho
Jorge S
JS
Williams
Richard D
RD
Mackay
Alan
A
Fenwick
Kerry
K
Grigoriadis
Anita
A
Ashworth
Alan
A
Pritchard-Jones
Kathy
K
Brown
Keith W
KW
Vujanic
Gordan M
GM
Jones
Chris
C
D001483:Base Sequence; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D018628:Gene Dosage; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D019656:Loss of Heterozygosity; D008969:Molecular Sequence Data; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009396:Wilms Tumor / Q000235:genetics* / Q000378:metabolism
C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II