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

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

Author information

  • 1Paediatric Oncology, Institute of Cancer Research/Royal Marsden NHS Trust, Sutton, United Kingdom.

Abstract

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.

PMID:
19047088
[PubMed - indexed for MEDLINE]
PMCID:
PMC2659869
Free PMC Article

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