Loss of heterozygosity at 7p in Wilms' tumour development

Chromosome 7p alterations have been implicated in the development of Wilms' tumour (WT) by previous studies of tumour cytogenetics, and by our analysi s of a constitutional translocation (t(1;7)(q42;p15)) in a child with Wi an d radial aplasia. We therefore used polymorphic microsatellite markers on 7 p for a loss of heterozygosity (LOH) study, and found LOH in seven out of 7 7 informative WTs (9%). The common region of LOH was 7p15-7p22, which conta ins the region disrupted by the t(1;7) breakpoint. Four WTs with 7p LOH had other genetic changes; a germline WT1 mutation with 11p LOH, LOH at 11p, L OH at 16q, and loss of imprinting of IGF2. Analysis of three tumour-associa ted lesions from 7p LOH cases revealed a cystic nephroma-like area also hav ing 7p LOH. However, a nephrogenic rest and a contralateral WT from the two other cases showed no 7p LOH. No particular clinical phenotype was associa ted with the WTs which showed 7p LOH. The frequency and pattern of 7p LOH d emonstrated in our studies indicate the presence of a tumour suppressor gen e at 7p involved in the development of Wilms' tumour. (C) 2000 Cancer Resea rch Campaign.