title: WT1 exon 1 deletion/insertion mutations in Wilms tumor patients, associated with di- and trinucleotide repeats and deletion hotspot consensus sequences.
abstract: The WT1 gene is known to play a role in at least some cases of Wilms tumor (WT). The first exon of the gene is highly GC rich and contains many short tandem di- and trinucleotide repeats, interrupted direct repeats, and CCTG (CAGG) motifs that have been identified as hotspots for DNA deletions. We have analyzed 80 WT patient samples for mutations in the first exon of WT1, either by SSCP analysis of the first 131 bp of the coding portion of WT1 exon 1 or by size analysis of a PCR product encompassing the coding region of exon 1 in addition to flanking noncoding regions. We report here the occurrence of somatic and germ-line deletion and insertion mutations in this portion of the gene in four WT patients. The mutations are flanked by short direct repeats, and the breakpoints are within 5 nt of a CCTG (CAGG) sequence. These data suggest that a distinctive mutational mechanism, previously unrecognized for this gene, is important for the generation of DNA mutations at the WT1 locus.
authors: Department of Experimental Pediatrics, University of Texas M.D. Anderson Cancer Center, Houston.
authors: V
authors: V
authors: Huff
authors: N
authors: N
authors: Jaffe
authors: G F
authors: GF
authors: Saunders
authors: L C
authors: LC
authors: Strong
authors: F
authors: F
authors: Villalba
authors: E C
authors: EC
authors: Ruteshouser
mesh_terms: D001483:Base Sequence; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons; D005260:Female; D016162:Genes, Wilms Tumor; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D018598:Minisatellite Repeats; D008969:Molecular Sequence Data; D017384:Sequence Deletion; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm