MBD1, MBD2 and CGBP genes at chromosome 18q21 are infrequently mutated in human colon and lung cancers

Scott Bader, Marion Walker, Heather A McQueen, Robert Sellar, Elizabeth Oei, Suzan Wopereis, Yanhua Zhu, Audrey Peter, Adrian P Bird, David J Harrison

Research output: Contribution to journalArticlepeer-review

Abstract

The genes MBD1 and MBD2 encode methyl-CpG binding proteins that suppress transcription from methylated promoters. In contrast, CGBP encodes a protein that binds promoters containing unmethylated CpG and stimulates transcription. All three are located on human chromosome 18q21, a region of frequent loss of heterozygosity in several cancers. These genes therefore represent candidate tumour suppressor genes, whose loss of function could affect the normal regulation of gene expression, whether by lack of complete suppression of genes normally silenced (via loss of MBD1 and MBD2) or by some loss of activation of genes normally expressed (via loss of CGBP), either way contributing to the tumorigenic phenotype. We have confirmed by fluorescent in situ hybridization that MBD1 and MBD2 bracket the DCC locus giving a gene order of MBD1/CGBP-DCC 5'-DCC 3'-MBD2. Mutation analyses by single-stranded conformation polymorphism in colon and lung cancer cell lines and primary tumours revealed a small number of mutations, suggesting only a limited role of these genes in human tumorigenesis.
Original languageEnglish
Pages (from-to)3506-10
Number of pages5
JournalOncogene
Volume22
Issue number22
DOIs
Publication statusPublished - 29 May 2003

Keywords

  • Chromosomes, Human, Pair 18
  • Colonic Neoplasms
  • CpG Islands
  • DNA Methylation
  • DNA-Binding Proteins
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms
  • Mutation
  • Repressor Proteins
  • Transcription Factors

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