title: A sporadic breast tumor with a somatically acquired complex genomic rearrangement in BRCA1.
abstract: Germ-line mutations in BRCA1 cause a substantial proportion of inherited breast cancer, and most result in inactivated BRCA1 proteins upon translation. Tumours developing in BRCA1 mutation carriers generally show loss of the wild-type allele. However, acquired inactivating mutations in BRCA1 in non-inherited breast tumours showing loss of heterozygosity at the gene locus have not been detected so far. Here we provide evidence that such mutations can be detected in a small proportion of breast tumours. Prompted by recent reports of Alu-mediated large genomic rearrangements in BRCA1, we have investigated whether such rearrangements might occur in sporadic breast cancer as well and have been missed thus far by traditional PCR-based mutation screening technology. To this end, we performed Southern blot analysis of 81 apparently sporadic breast tumours using probes covering exons 6-24 and 3 restriction enzymes. We identified 1 case with an acquired rearrangement (1.2%), indicating that BRCA1 inactivation through changes in the primary genomic sequence of the gene is uncommon in breast cancer. Genes Chromosomes Cancer 27:295-302, 2000.
authors.affiliation: Department of Molecular Biology, National Institute of Oncology, Budapest, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: van der Looij
authors.forename: A M
authors.initials: AM
authors.lastname: Cleton-Jansen
authors.forename: R
authors.initials: R
authors.lastname: van Eijk
authors.forename: H
authors.initials: H
authors.lastname: Morreau
authors.forename: M
authors.initials: M
authors.lastname: van Vliet
authors.forename: N
authors.initials: N
authors.lastname: Kuipers-Dijkshoorn
authors.forename: E
authors.initials: E
authors.lastname: Oláh
authors.forename: C J
authors.initials: CJ
authors.lastname: Cornelisse
authors.forename: P
authors.initials: P
authors.lastname: Devilee
mesh_terms: D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D005819:Genetic Markers; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D016133:Polymerase Chain Reaction
chemical_list: D019313:BRCA1 Protein; D004273:DNA, Neoplasm; D005819:Genetic Markers