The genomic structure of the DMBT1 gene: evidence for a region with susceptibility to genomic instability

Oncogene. 1999 Nov 4;18(46):6233-40. doi: 10.1038/sj.onc.1203071.

Abstract

Increasing evidence has accumulated for an involvement of the inactivation of tumour suppressor genes at chromosome 10q in the carcinogenesis of brain tumours, melanomas, and carcinomas of the lung, the prostate, the pancreas, and the endometrium. The gene DMBT1 (Deleted in Malignant Brain Tumours 1) is located at chromosome 10q25.3-q26.1, within one of the putative intervals for tumour suppressor genes. DMBT1 is a member of the scavenger-receptor cysteine-rich (SRCR) superfamily and displays homozygous deletions or lack of expression in glioblastoma multiforme, medulloblastoma, and in gastrointestinal and lung cancers. Based on these properties, DMBT1 has been proposed to be a candidate tumour suppressor gene. We have determined the genomic sequence of DMBT1 to allow analyses of mutations. The gene has at least 54 exons that span a genomic region of about 80 kb. We have identified a putative exon with coding potential for a transmembrane domain. Our data further suggest that alternative splicing gives rise to isoforms of DMBT1 with a differential utilization of SRCR domains and SRCR interspersed domains. The major part of the gene harbours locus specific repeats. These repeats may point to the DMBT1 locus as a region susceptible to chromosomal instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agglutinins*
  • Amino Acid Sequence
  • Chromosomes, Human, Pair 10 / genetics*
  • Exons / genetics
  • Genes*
  • Genes, Tumor Suppressor*
  • Humans
  • Molecular Sequence Data
  • Multigene Family
  • Neoplasms / genetics
  • RNA Splicing
  • Receptors, Cell Surface / genetics*
  • Repetitive Sequences, Nucleic Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Sequence Deletion
  • Sequence Homology, Amino Acid

Substances

  • Agglutinins
  • DMBT1 protein, human
  • Receptors, Cell Surface