title: MBD1, MBD2 and CGBP genes at chromosome 18q21 are infrequently mutated in human colon and lung cancers.
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.
authors.affiliation: Sir Alastair Currie Cancer Research UK Laboratories, Division of Pathology Molecular Medicine Centre, University of Edinburgh, Edinburgh EH4 2XU, UK. s.bader@ed.ac.uk
authors.forename: Scott
authors.initials: S
authors.lastname: Bader
authors.forename: Marion
authors.initials: M
authors.lastname: Walker
authors.forename: Heather A
authors.initials: HA
authors.lastname: McQueen
authors.forename: Robert
authors.initials: R
authors.lastname: Sellar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Oei
authors.forename: Suzan
authors.initials: S
authors.lastname: Wopereis
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Zhu
authors.forename: Audrey
authors.initials: A
authors.lastname: Peter
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Bird
authors.forename: David J
authors.initials: DJ
authors.lastname: Harrison
mesh_terms: D002887:Chromosomes, Human, Pair 18; D003110:Colonic Neoplasms / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics*; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics*; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; C066141:MBD1 protein, human; C115368:MBD2 protein; C489325:MBD2 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors