Refinement within single yeast artificial chromosome clones of a minimal region commonly deleted on the short arm of chromosome 7 in Wilms tumours

Cytogenetic and molecular data indicate an involvement of genes mapped to t he proximal portion of the short arm of chromosome 7 (7p) in Wilms tumours (WTs). We have analysed 38 WTs using a panel of eight microsatellite marker s mapped to proximal 7p. Loss of heterozygosity (LOH) in tumour, compared w ith matched constitutional DNA, was identified in eight cases. To define be tter the minimal region commonly deleted in these tumours, they were analys ed with nine additional markers, mapped within the region of interest. One tumour (case 30) showed LOH for only one marker (D7S510), while maintaining heterozygosity for the two immediately flanking loci (07S555 and D7S668). This result was confirmed by fluorescence in situ hybridisation analysis, w hich showed that in the majority (65%) of nuclei from tumour 30 hybridising with a bacterial artificial chromosome clone containing the D7S510 locus, only one signal was visible. Noticeably, both markers defining the limits o f the observed deleted region are simultaneously present within two distinc t overlapping yeast artificial chromosome (YAC) clones mapped to chromosome bands 7p13-p14. This suggests that the maximum length of the missing DNA f ragment was approximately 1.3 Mb, corresponding to the length of the smalle r of the two YAC clones. In all other cases that showed LOH, the deletion e ncompassed the 7p13-p14 region. For this reason, we speculate that the iden tified interval contains a gene whose inactivation is important for the dev elopment of at least a fraction of WTs. (C) 2001 Wiley-Liss, Inc.