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

Vuononvirta, Raisa, Sebire, Neil J., Dallosso, Anthony R., Reis-Filho, Jorge S., Williams, Richard D., Mackay, Alan, Fenwick, Kerry, Grigoriadis, Anita, Ashworth, Alan, Pritchard-Jones, Kathy, Brown, Keith W., Vujanic, Gordan and Jones, Chris 2008. Perilobar nephrogenic rests are nonobligate molecular genetic precursor lesions of insulin-like growth factor-II-associated Wilms tumors. Clinical Cancer Research 14 (23) , pp. 7635-7644. 10.1158/1078-0432.CCR-08-1620

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: Wilms tumor; perilobar nephrogenic rest; aCGH; IGF-II; LOI; LOH
Publisher: American Association for Cancer Research
ISSN: 1078-0432
Funders: Cancer Research UK, Breakthrough Breast Cancer, CLIC Sargent, University of Bristol Cancer Research Fund
Last Modified: 04 Jun 2017 04:21
URI: http://orca.cf.ac.uk/id/eprint/37546

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