The familial Wilms' tumour susceptibility gene, FWT1, may not be a tumour suppressor gene

Oncogene. 1997 Jun 26;14(25):3099-102. doi: 10.1038/sj.onc.1201107.

Abstract

A familial Wilms' tumour susceptibility gene, known as FWT1, has recently been localised to chromosome 17q12-q21 by genetic linkage analysis. Four Wilms' tumours from a family showing strong evidence of linkage to FWT1 were examined for allele loss using polymorphic microsatellite markers on chromosome 17q. In three tumours no loss of heterozygosity was observed. In the remaining case, loss of heterozygosity was detected at all markers analysed. However, the alleles lost in this Wilms' tumour were those segregating with the disease in the family. This is in contrast to the usual pattern observed in familial cancer syndromes, where the allele lost in tumours arising in gene carriers is the wild type inherited from the non mutation carrying parent. Taken together with previous data indicating that LOH on chromosome 17q is rare in sporadic Wilms' tumour, the results suggest that FWT1 is not a tumour suppressor gene. Moreover, loss of alleles linked to the disease and the implied absence of the mutated susceptibility gene in one tumour, suggests that a mutation in FWT1 may be necessary for the initiation of some familial Wilms' tumours but subsequently the maintenance of the neoplastic phenotype becomes independent of the FWT1 mutation.

MeSH terms

  • Alleles
  • Chromosomes, Human, Pair 11
  • Genes, Tumor Suppressor*
  • Genes, Wilms Tumor*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Mutation
  • Polymerase Chain Reaction
  • Wilms Tumor / genetics*

Substances

  • Genetic Markers