Analysis by array CGH of genomic changes associated with the progression or relapse of Wilms' tumour.
Despite aggressive salvage regimens, approximately half of all children who suffer a Wilms' tumour recurrence will die of their disease. Although there are increasing data on molecular genetic prognostic factors present in the tumour at diagnosis, there is little information regarding the molecular events that occur with Wilms' tumour progression and relapse. In the present study, microarray-based comparative genomic hybridization (aCGH) analysis has been carried out on 58 Wilms' tumour samples, which included 38 untreated primary and 20 recurrent tumours. A higher degree of copy number changes was observed in the recurrent tumours (33.0% genomic clones) than in the primary tumour (21.2%). Paired analysis highlighted the acquisition of 15q gain with high levels of IGF1R expression in the tumour recurrence in two cases. The most statistically significant abnormality acquired between diagnosis and relapse was loss of 17p. One case that experienced 17p loss was classified as favourable histology at diagnosis, but exhibited diffuse anaplasia at recurrence and had a homozygous TP53 deletion. Another instructive case with a constitutional 11p13 deletion presented with bilateral tumours and suffered two subsequent recurrences in the left kidney. A somatic WT1 mutation was found only in the right kidney tumour, while the constitutional 11p13 deletion was the only abnormality detected in the initial left kidney tumour by aCGH. The two subsequent relapses in the left kidney contained an accumulation of additional genetic alterations, including an independent WT1 mutation.
Natrajan
R
R
Paediatric Oncology, Institute of Cancer Research/Royal Marsden NHS Trust, Sutton, UK.
Little
S E
SE
Sodha
N
N
Reis-Filho
J S
JS
Mackay
A
A
Fenwick
K
K
Ashworth
A
A
Perlman
E J
EJ
Dome
J S
JS
Grundy
P E
PE
Pritchard-Jones
K
K
Jones
C
C
D015783:Aniridia / Q000150:complications / Q000235:genetics; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D016162:Genes, Wilms Tumor; D016158:Genes, p53; D006720:Homozygote; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009396:Wilms Tumor / Q000150:complications / Q000235:genetics* / Q000473:pathology