Genomic rearrangement screening of the BRCA1 from seventy Iranian high-risk breast cancer families

Abstract

Background: Th e second leading cause of cancer deaths in women is breast cancer. Germline mutations in susceptibility breast cancer gene BRCA1 increase the lifetime risk of breast cancer. Eighty-one large genomic rearrangements (LGRs) have been reported up to date in BRCA1 gene, and evaluation of these rearrangements helps with precise risk assessment in high-risk individuals. In this study, we have investigated LGRs in BRCA1 among Iranian high-risk breast cancer families. Materials and Methods: Seventy patients with breast cancer who were identifi ed negative for point mutations or small deletions/insertions of BRCA1 gene were selected. Deletions and duplications of BRCA1 gene were evaluated using multiplex ligation-dependent probe amplifi cation (MLPA).Results: Two deletions, deletion of exons 1A/1B-2 and exon 24, were detected in two patients with breast cancer. Th e former alteration was found in a woman with a strong family history of breast cancer while the latter one was detected in a woman with early onset of breast cancer. Conclusion: Although our data confi rm that LGRs in BRCA1 comprise a relatively small proportion of mutations in hereditary breast cancer in the Iranian population, MLPA analysis might be considered for screening of LGRs in high-risk individuals.It is worth to note that our results are consistent with previous studies in various Asian and European countries.

Key words: BRCA1 gene, breast cancer, large genomic rearrangements, multiplex ligation-dependent probe amplifi cation