Open Access Open Badges Research article

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

Amanda Gonçalves Silva12, Ingrid Petroni Ewald34, Marina Sapienza5, Manuela Pinheiro6, Ana Peixoto6, Amanda França de Nóbrega1, Dirce M Carraro12, Manuel R Teixeira67, Patricia Ashton-Prolla348, Maria Isabel W Achatz12, Carla Rosenberg25 and Ana C V Krepischi129*

Author Affiliations

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

2 National Institute of Science and Technology in Oncogenomics, São Paulo, Brazil

3 Experimental Research Center Hospital de Clínicas de Porto Alegre, Rio Grande do Sul, Brazil

4 Post-Graduate Course in Medicine, Medical Sciences, Federal University of Rio Grande do Sul, Porto Alegre, Brazil

5 Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil

6 Department of Genetics, Portuguese Oncology Institute, Porto, Portugal

7 Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal

8 Department of Genetics and Post-Graduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul and Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

9 Hospital A. C. Camargo, Rua Taguá, 440 – Liberdade – CEP 01508-010, São Paulo, Brazil

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BMC Cancer 2012, 12:237  doi:10.1186/1471-2407-12-237

Published: 12 June 2012



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.


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.


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.


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.

Breast cancer; Copy number variation; MLPA; BRCA1 microdeletion; Li-Fraumeni syndrome