title: Mutation analysis of the MDM4 gene in German breast cancer patients.
abstract: BACKGROUND
  MDM4 is a negative regulator of p53 and cooperates with MDM2 in the cellular response to DNA damage. It is unknown, however, whether MDM4 gene alterations play some role in the inherited component of breast cancer susceptibility.
  
  
  METHODS
  We sequenced the whole MDM4 coding region and flanking untranslated regions in genomic DNA samples obtained from 40 German patients with familial breast cancer. Selected variants were subsequently screened by RFLP-based assays in an extended set of breast cancer cases and controls.
  
  
  RESULTS
  Our resequencing study uncovered two MDM4 coding variants in 4/40 patients. Three patients carried a silent substitution at codon 74 that was linked with another rare variant in the 5'UTR. No association of this allele with breast cancer was found in a subsequent screening of 133 patients with bilateral breast cancer and 136 controls. The fourth patient was heterozygous for the missense substitution D153G which is located in a less conserved region of the MDM4 protein but may affect a predicted phosphorylation site. The D153G substitution only partially segregated with breast cancer in the family and was not identified on additional 680 chromosomes screened.
  
  
  CONCLUSIONS
  This study did not reveal clearly pathogenic mutations although it uncovered two new unclassified variants at a low frequency. We conclude that there is no evidence for a major role of MDM4 coding variants in the inherited susceptibility towards breast cancer in German patients.
authors.affiliation: Department of Gynaecology and Obstetrics, Hannover Medical School, Carl-Neuberg Str, 1, 30625 Hannover, Germany. doerk.thilo@mh-hannover.de
authors.forename: Scarlett
authors.initials: S
authors.lastname: Reincke
authors.forename: Lina
authors.initials: L
authors.lastname: Govbakh
authors.forename: Bettina
authors.initials: B
authors.lastname: Wilhelm
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jin
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.forename: Michael
authors.initials: M
authors.lastname: Bremer
authors.forename: Johann H
authors.initials: JH
authors.lastname: Karstens
authors.forename: Thilo
authors.initials: T
authors.lastname: Dörk
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005820:Genetic Testing; D005858:Germany; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins