title: Analysis of BRCA1, TP53, and TSG101 germline mutations in German breast and/or ovarian cancer families.
abstract: About 5%-10% of breast cancers are considered to be hereditary and associated with germline mutations of specific genes. As yet, the most frequently affected genes identified are BRCA1 and BRCA2, but also other genes such as TP53 are supposed to influence the predisposition toward breast cancer. In the present study, we analyzed patients of 19 German families with early onset breast cancer and/or a family history of breast and/or ovarian cancer for the presence of mutations in BRCA1 and TP53. In addition, we screened for germline mutations in the putative tumor suppressor gene TSG101. For this purpose we used direct sequence analysis of the entire coding regions for all three genes and, in the case of BRCA1, single-strand conformation polymorphism analysis and protein transcription-translation assays. We identified eight previously described polymorphisms and several aberrations in BRCA1: 1 unclassified missense mutation, 3 small protein truncating mutations, 1 novel pseudoexon, and 5 splicing variants. No mutation was detected in TP53. Analysis of TSG101 transcripts revealed an aberrant transcript in two breast cancer patients belonging to the same family, suggesting TSG101 as a predisposing gene in hereditary breast cancer.
authors.affiliation: Department of Otorhinolaryngology, Heinrich-Heine-University, Moorenstr. 5, D-40225, Düsseldorf, Germany. balz@uni-duesseldorf.de
authors.forename: Vera
authors.initials: V
authors.lastname: Balz
authors.forename: Hans Bernd
authors.initials: HB
authors.lastname: Prisack
authors.forename: Henning
authors.initials: H
authors.lastname: Bier
authors.forename: Hans
authors.initials: H
authors.lastname: Bojar
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D056827:Endosomal Sorting Complexes Required for Transport; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D000099177:Tsg101 Protein
chemical_list: D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000099177:Tsg101 Protein