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BMC Cancer. 2012 Jun 12;12:237. doi: 10.1186/1471-2407-12-237.

Li-Fraumeni-like syndrome associated with a large BRCA1 intragenic deletion.

Author information

1
International Center for Research and Training, A. C. Camargo Cancer Hospital, São Paulo, Brazil.

Abstract

BACKGROUND:

Li-Fraumeni (LFS) and Li-Fraumeni-like (LFL) syndromes are associated to germline TP53 mutations, and are characterized by the development of central nervous system tumors, sarcomas, adrenocortical carcinomas, and other early-onset tumors. Due to the high frequency of breast cancer in LFS/LFL families, these syndromes clinically overlap with hereditary breast cancer (HBC). Germline point mutations in BRCA1, BRCA2, and TP53 genes are associated with high risk of breast cancer. Large rearrangements involving these genes are also implicated in the HBC phenotype.

METHODS:

We have screened DNA copy number changes by MLPA on BRCA1, BRCA2, and TP53 genes in 23 breast cancer patients with a clinical diagnosis consistent with LFS/LFL; most of these families also met the clinical criteria for other HBC syndromes.

RESULTS:

We found no DNA copy number alterations in the BRCA2 and TP53 genes, but we detected in one patient a 36.4 Kb BRCA1 microdeletion, confirmed and further mapped by array-CGH, encompassing exons 9-19. Breakpoints sequencing analysis suggests that this rearrangement was mediated by flanking Alu sequences.

CONCLUSION:

This is the first description of a germline intragenic BRCA1 deletion in a breast cancer patient with a family history consistent with both LFL and HBC syndromes. Our results show that large rearrangements in these known cancer predisposition genes occur, but are not a frequent cause of cancer susceptibility.

PMID:
22691290
PMCID:
PMC3502571
DOI:
10.1186/1471-2407-12-237
[Indexed for MEDLINE]
Free PMC Article
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