A sporadic breast tumor with a somatically acquired complex genomic rearrangement in BRCA1

Genes Chromosomes Cancer. 2000 Mar;27(3):295-302. doi: 10.1002/(sici)1098-2264(200003)27:3<295::aid-gcc10>3.0.co;2-f.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • BRCA1 Protein / genetics
  • Blotting, Southern
  • Breast Neoplasms / genetics*
  • DNA, Neoplasm / genetics
  • Female
  • Genes, BRCA1*
  • Genetic Markers
  • Germ-Line Mutation
  • Humans
  • Loss of Heterozygosity
  • Polymerase Chain Reaction


  • BRCA1 Protein
  • DNA, Neoplasm
  • Genetic Markers