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

Grundy, Richard G.; Pritchard, John; Scambler, Peter J.; Cowell, John K.

doi:10.1038/sj.onc.1201927

Cited by 42 publications

(35 citation statements)

References 35 publications

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“…Our results are the largest study so far of 7p LOH in WT, and our 9% LOH rate is very similar to the 10% (four out of 40) reported recently by Grundy et al (1998), but less than the 27% (three out of 11) found by Miozzo et al (1996). The common region of LOH in our study was between D7S683 and D7S517 (7p15-7p22), which overlaps with the minimal LOH regions identified by Grundy et al (D7S503-D7S517) and (Figure 1) (Miozzo et al, 1996;Grundy et al, 1998).…”

Section: supporting

confidence: 75%

“…The common region of LOH in our study was between D7S683 and D7S517 (7p15-7p22), which overlaps with the minimal LOH regions identified by Grundy et al (D7S503-D7S517) and (Figure 1) (Miozzo et al, 1996;Grundy et al, 1998). However, the minimal regions defined in these latter reports are separated by approximately 15 cM (Dib et al, 1996), with the common region defined by Grundy et al being distal to that reported by Miozzo et al In addition, Grundy et al identified a putative homozygous deletion at D7S507 (7p15/p21) in one tumour (Grundy et al, 1998), which lies approximately 25 cM distal to the constitutional t(1;7) breakpoint which we have mapped in our WT patient (Reynolds et al, 1996). Thus it seems likely that there may be two loci on 7p involved in the development of Wilms' tumour; one at 7p15 and another more distal.…”

Section: mentioning

confidence: 51%

“…In contrast, Grundy et al (1998) have suggested that tumours with 7p abnormalities tend to be of early onset and of high stage. Clearly larger numbers of tumours need to be studied, but if there are two WT loci on 7p, then distinct phenotypes may be associated with each locus, complicating the analysis of clinical data when genetic abnormalities have only been defined by LOH.…”

Section: mentioning

confidence: 97%

“…Grundy et al (1998) reported that 11p LOH had been previously identified in one of their WTs with 7p LOH, and others have found chromosome 7 cytogenetic abnormalities in association with a chromosome 11 deletion (Wang-Wuu et al, 1990), and with a germline WT1 mutation and 11p LOH (Lobbert et al, 1998). Thus Other details as in Figure 1.…”

Section: mentioning

confidence: 99%

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Loss of heterozygosity at 7p in Wilms’ tumour development

et al. 2000

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Chromosome 7p alterations have been implicated in the development of Wilms' tumour (WT) by previous studies of tumour cytogenetics, and by our analysis of a constitutional translocation (t(1;7)(q42;p15)) in a child with WT and radial aplasia. We therefore used polymorphic microsatellite markers on 7p for a loss of heterozygosity (LOH) study, and found LOH in seven out of 77 informative WTs (9%). The common region of LOH was 7p15–7p22, which contains 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, LOH at 16q, and loss of imprinting of IGF2 . Analysis of three tumour-associated lesions from 7p LOH cases revealed a cystic nephroma-like area also having 7p LOH. However, a nephrogenic rest and a contralateral WT from the two other cases showed no 7p LOH. No particular clinical phenotype was associated with the WTs which showed 7p LOH. The frequency and pattern of 7p LOH demonstrated in our studies indicate the presence of a tumour suppressor gene at 7p involved in the development of Wilms' tumour. © 2000 Cancer Research Campaign

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Section: supporting

confidence: 75%

Section: mentioning

confidence: 51%

Section: mentioning

confidence: 97%

Section: mentioning

confidence: 99%

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Loss of heterozygosity at 7p in Wilms’ tumour development

et al. 2000

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“…The existence of Wilms tumor families for which linkage to both FWT1 and FWT2 has been excluded indicates the existence of at least one additional FWT gene (Ruteshouser and Huff, 2004). Other loci,including 11p15,1p,2q,7p,9q,14q,16q,and 22, have also been implicated in the etiology of Wilms tumor through studies of loss of heterozygosity, loss of imprinting, and constitutional chromosomal defects (Mannens et al, 1990;Kaneko et al, 1991;Maw et al, 1992;Olson et al, 1995;Grundy et al, 1998;Ruteshouser et al, 2005). CTNNB1, the gene encoding β-catenin, is also mutated in about 15% of Wilms tumors (Koesters et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Wilms tumor genetics: Mutations in WT1, WTX, and CTNNB1 account for only about one‐third of tumors

Ruteshouser¹,

Robinson²,

Huff³

2008

Genes Chromosomes & Cancer

181

149

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Wilms tumor is genetically heterogeneous, and until recently only one Wilms tumor gene was known, WT1 at 11p13. However, WT1 is altered in only ~20% of Wilms tumors. Recently a novel gene, WTX at Xq11.1, was reported to be mutated in Wilms tumors. No overlap between tumors with mutations in WTX and WT1 was noted, suggesting that WT1 and WTX mutations could account for the genetic basis of roughly half of Wilms tumors. To assess the frequency of WTX mutations and their relationship to WT1 mutations in a larger (n = 125) panel of Wilms tumors which had been thoroughly assessed for mutations in WT1, we conducted a complete mutational analysis of WTX that included sequencing of the entire coding region and quantitative PCR to identify deletions of the WTX gene. Twenty-three (18.4%) tumors carried a total of 24 WTX mutations, a lower WTX mutation frequency than that previously observed. Surprisingly, we observed an equivalent frequency of WTX mutations in tumors with mutations in either or both WT1 and CTNNB1 (20.0%) and tumors with no mutation in either WT1 or CTNNB1 (17.5%). WTX has been reported to play a role in the WNT/β-catenin signaling pathway, and, interestingly, WTX deletion/truncation mutations appeared to be rare in tumors carrying exon 3 mutations of CTNNB1, encoding β-catenin. Our findings indicate that WT1 and WTX mutations occur with similar frequency, that they partially overlap in Wilms tumors, and that mutations in WT1, WTX, and CTNNB1 underlie the genetic basis of about one-third of Wilms tumors.

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