Abstract 2595: Screening for genomic rearrangements in BRCA1 and BRCA2 genes in Algerian breast/ovarian cancer families

Abstract Background: Breast cancer is the leading cause of cancer death in women in Algeria. To date, few molecular genetics studies of BRCA1 and BRCA2 germline mutations have been reported in the Algerian population. The most frequent mutations encountered in BRCA genes are deletions or insertions of a few bases or single-base substitutions that result in premature stop codons. However, an increasing number of large genomic rearrangements (LGRs) have been identified especially in BRCA1 gene, whereas the frequency of genomic rearrangements in BRCA2 gene is low in many populations. The objective of our study was to characterize genomic rearrangements in 76 Algerian breast/ovarian cancer patients and relatives tested negative for small point mutations in BRCA1 and BRCA2 genes. Methods: MLPA was performed on genomic DNA as described by Schouten et al (2002). Screening for genomic rearrangements in BRCA1 and BRCA2 genes of 76 patients and relatives were performed by using MLPA commercial kits P002-B1, P087-B1 and PO45-B2, PO90-B2 respectively (MRC-Holland, Amsterdam, The Netherlands). To confirm the rearrangement and to determine the exact site of its genomic breakpoints, we performed long-range PCR of genomic DNA using the Expand Long Template PCR System (Roche Diagnostics GmbH, Mannheim, Germany). Results: MLPA analysis of the BRCA1 gene revealed two germline alterations in two unrelated patients among 76. A novel deletion of BRCA1 exon 2 (c.-19-α_80+−del/p.α) and a novel genomic breakpoint in deletion of BRCA1 exon 8 (c.442-α_547+−del/p≤) were identified in two patients with breast/ovarian cancer and bilateral breast cancer, respectively. No LGRs were detected in BRCA2 gene. We found by using Long range PCR technique that our patient with the BRCA1 exon 8 deletion is heterozygous for a 2.6 kb deletion. Investigations aimed at determining the genomic breakpoint of the BRCA1 exon 2 deletion described in our study is on going. Conclusion: For the first time, we report here two genomic rearrangements in BRCA1 gene in Algerian breast/ovarian cancer patients. Our results reinforce the idea that breast/ovarian cancer families tested negatively for small point mutations should be routinely screened with MLPA for large genomic rearrangements in BRCA1 and BRCA2 genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2595. doi:1538-7445.AM2012-2595