Data from <i>BRCA1</i> Mutation Analysis of 41 Human Breast Cancer Cell Lines Reveals Three New Deleterious Mutants

Abstract

<div>Abstract<p>Germ line mutations of the <i>BRCA1</i> gene confer a high risk of breast cancer and ovarian cancer to female mutation carriers. The BRCA1 protein is involved in the regulation of DNA repair. How specific tumor-associated mutations affect the molecular function of BRCA1, however, awaits further elucidation. Cell lines that harbor <i>BRCA1</i> gene mutations are invaluable tools for such functional studies. Up to now, the HCC1937 cell line was the only human breast cancer cell line with an identified <i>BRCA1</i> mutation. In this study, we identified three other <i>BRCA1</i> mutants from among 41 human breast cancer cell lines by sequencing of the complete coding sequence of <i>BRCA1</i>. Cell line MDA-MB-436 had the 5396 + 1G>A mutation in the splice donor site of exon 20. Cell line SUM149PT carried the 2288delT mutation and SUM1315MO2 carried the 185delAG mutation. All three mutations were accompanied by loss of the other <i>BRCA1</i> allele. The 185delAG and 5396 + 1G>A mutations are both classified as pathogenic mutations. In contrast with wild-type cell lines, none of the <i>BRCA1</i> mutants expressed nuclear BRCA1 proteins as detected with Ab-1 and Ab-2 anti-BRCA1 monoclonal antibodies. These three new human <i>BRCA1</i> mutant cell lines thus seem to be representative breast cancer models that could aid in further unraveling of the function of BRCA1. (Cancer Res 2006; 66(1): 41-5)</p></div>