The parathyroid hormone-responsive B1 gene is interrupted by a t(1;7)(q42;p15) breakpoint associated with Wilms' tumour

Oncogene. 2003 Mar 6;22(9):1371-80. doi: 10.1038/sj.onc.1206332.

Abstract

Wilms' tumour (WT) has a diverse and complex molecular aetiology, with several different loci identified by cytogenetic and molecular analyses. One such locus is on chromosome 7p, where cytogenetic abnormalities and loss of heterozygosity (LOH) indicate the presence of a Wilms' tumour suppressor gene. In order to isolate a candidate gene for this locus, we have characterized the breakpoint regions at a novel constitutional chromosome translocation (t(1;7)(q42;p15)), found in a child with WT and skeletal abnormalities. We identified two genes that were interrupted by the translocation: the parathyroid hormone-responsive B1 gene (PTH-B1) at 7p and obscurin at 1q. With no evidence for LOH at 1q42, we focused on the characterization of PTH-B1. We detected novel alternately spliced isoforms of PTH-B1, which were expressed in a wide range of adult and foetal tissues. Importantly, expression of two isoforms were disrupted in the WT of the t(1;7) patient. We also identified an additional splice isoform expressed only in 7p LOH tumours. The disruption of PTH-B1 by the t(1;7), together with aberrant splicing in sporadic WTs, suggests that PTH-B1 is a candidate for the 7p Wilms' tumour suppressor gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Base Sequence
  • Child
  • Chromosome Breakage
  • Chromosome Mapping
  • Chromosomes, Artificial, Yeast
  • Chromosomes, Human, Pair 1 / genetics*
  • Chromosomes, Human, Pair 7 / genetics*
  • Cytoskeletal Proteins
  • Expressed Sequence Tags
  • Fetal Proteins / analysis
  • Genes, Tumor Suppressor*
  • Guanine Nucleotide Exchange Factors / genetics
  • Humans
  • Kidney / abnormalities
  • Kidney / embryology
  • Kidney Neoplasms / genetics*
  • Loss of Heterozygosity
  • Molecular Sequence Data
  • Monosomy
  • Muscle Proteins / genetics
  • Neoplasm Proteins
  • Organ Specificity
  • Protein Isoforms / genetics
  • Protein Serine-Threonine Kinases
  • Proteins / analysis
  • Proteins / chemistry
  • Proteins / genetics*
  • Rho Guanine Nucleotide Exchange Factors
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Translocation, Genetic*
  • Trisomy
  • Wilms Tumor / genetics*

Substances

  • BBS9 protein, human
  • Cytoskeletal Proteins
  • Fetal Proteins
  • Guanine Nucleotide Exchange Factors
  • Muscle Proteins
  • Neoplasm Proteins
  • Protein Isoforms
  • Proteins
  • Rho Guanine Nucleotide Exchange Factors
  • OBSCN protein, human
  • Protein Serine-Threonine Kinases