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Breast Cancer Res Treat. 2008 Nov;112(1):63-7. Epub 2007 Dec 1.

Identification of a novel BRCA1 large genomic rearrangement in a Spanish breast/ovarian cancer family.

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1
Laboratorio de Biología Molecular del Servicio de Biopatología Clínica, Escuela de Enfermería 7a planta, Hospital Universitario La Fe, Avd. Campanar 21, 46009, Valencia, Spain.

Abstract

BACKGROUND:

Alterations in BRCA1 gene are responsible for the majority of hereditary breast and/or ovarian cancers. However, the frequency of detected germline mutations is lower than expected by linkage analysis. Standard PCR-based screening methods are mainly used for detecting mutations, but the large genomic rearrangements are commonly overlooked. The purpose of this study was to confirm and characterize a novel deletion identified in BRCA1 gene which has not yet been reported to date.

METHODS:

Multiplex ligation-dependent probe amplification was used to analyze BRCA1 rearrangements in 255 unrelated index patients with familial breast and/or ovarian cancer negative for BRCA1/BRCA2 mutations studied in Program of Genetic Counselling on Cancer of Valencia Community (Spain). The breakpoints of detected novel rearrangement were characterized by sequencing.

RESULTS AND DISCUSSION:

Five different rearrangements in the BRCA1 gene were identified in five unrelated index patients out of the 225 (2%). We found four large genomic rearrangements already described consisting in a 1A/1B and 2 deletion; deletion of exons 5-7; deletion of exons 8-13; exon 20 deletion. Additionally, we found the novel g.8097_22733del14637 deletion that encompasses exons 3-5. This deletion affects the RING domain of the BRCA1 protein and it is suggestive of having a negative impact on its function.

CONCLUSION:

The new mutation here reported broadens the mutational spectrum of large rearrangements. Furthermore, the five large rearrangements found in patients non-carriers of BRCA1/BRCA2 mutations reinforce the need of studying BRCA1 large genomic rearrangements in genetic counselling programs.

PMID:
18060491
DOI:
10.1007/s10549-007-9839-6
[Indexed for MEDLINE]
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