TY - JOUR
T1 - Perilobar nephrogenic rests are nonobligate molecular genetic precursor lesions of insulin-like growth factor-II-associated Wilms tumors
AU - Vuononvirta, R
AU - Sebire, NJ
AU - Dallosso, AR
AU - Reis-Filho, JS
AU - Williams, RD
AU - Mackay, A
AU - Fenwick, K
AU - Grigoriadis, A
AU - Ashworth, A
AU - Pritchard-Jones, K
AU - Brown, KW
AU - Vujanic, G
AU - Jones, C
N1 - Publisher: American Association for Cancer Research
PY - 2008/12
Y1 - 2008/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-59449110723&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-08-1620
DO - 10.1158/1078-0432.CCR-08-1620
M3 - Article (Academic Journal)
C2 - 19047088
VL - 14
SP - 7635
EP - 7644
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
ER -