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

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. © 2000 Wiley‐Liss, Inc.