Mapping of a Putative Tumor Suppressor Locus to Proximal 7p in Wilms Tumors

Loss of heterozygosity for the short arm of chromosome 7 in sporadic Wilms tumour

“…The constitutional breakpoint in this patient therefore lies distal to the homozygous deletion in GOS 44. LOH for markers on 7p have also been reported in other sporadic Wilms tumours (Wilmore et al, 1994;Miozzo et al, 1996). Wilmore et al (1994) analysed a series of 23 sporadic Wilms tumours for LOH of markers on 7p by Southern blot analysis, reporting LOH for the 7p14-pter region in a bilateral tumour and trisomy for chromosome 7 in two other unilateral tumours (Wilmore et al, 1994).…”

“…However, band 7p15 has also been implicated, ®rstly in a patient with a congenital t,(1;7) translocation who subsequently developed a Wilms tumour (Wilmore et al, 1994;Hewitt et al, 1991), and secondly from a Wilms tumour with the sole t,(7;7)(p13;q21) cytogenetic change which resulted in monosomy for 7p13-pter (Sawyer et al, 1993). The recent description of cytogenetic abnormalities involving the short arm chromosome 7 in 2/11 Wilms tumours, provides further evidence supporting the existence of a`tumour suppressor gene' in this chromosomal region (Miozzo et al, 1996). One of these tumours had a complex karyotype including a t(1;7)(p36;p15) and a deletion spanning 7p12-pter.…”

“…These ®ndings suggest that LOH in Wilms tumour is a non-random event occurring only in speci®c chromosomal regions. Cytogenetic studies have also implicated chromosome 7 in Wilms tumorigenesis (Rivera et al, 1985) and, in particular, suggest the presence of a tumour suppressor gene at 7p15 (Hewitt et al, 1991;Wilmore et al, 1994;Sawyer et al, 1993;Miozzo et al, 1996). We therefore analysed a series of sporadic Wilms tumours from a single institution for allelic loss on the short arm of chromosome 7.…”

“…Interestingly, this tumour had no detectable normal chromosome 7p material. The other tumour had an isochrome 7q in addition to trisomy for chromosomes 8, 9 and 13 (Miozzo et al, 1996). Further evidence for a Wilms tumour predisposition gene on 7p is provided by two children with a constitutional translocation involving the short arm of chromosome 7 and Wilms tumour.…”

Absence of PPP2R1A mutations in Wilms tumor

“…Approximately 1 ± 2% of Wilms tumors are familial (Breslow et al, 1993). The etiology of Wilms tumorigenesis is known to be complex, with four or more loci (WT1 at 11p13, FWT1 at 17q12-21, FWT2 at 19q13.4, and additional WT genes at 11p15, 1p, 7p, and/or 16q) implicated in the development of WT (Call et al, 1990;Gessler et al, 1990;Rahman et al, 1996;Hu et al, 1997;McDonald et al, 1998;Mannens et al, 1990;Maw et al, 1992;Miozzo et al, 1996). Thus far, WT1 at 11p13 is the only WT gene to be identi®ed and characterized.…”