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

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Silva, Amanda Goncalves ^[1] ; Ewald, Ingrid Petroni ^[2] ; Sapienza, Marina ^[3] ; Pinheiro, Manuela ^[4] ; Peixoto, Ana ^[5] ; de Nobrega, Amanda Frana ^[6] ; Carraro, Dirce M. ^[7] ; Teixeira, Manuel R. ^[8] ; Ashton-Prolla, Patricia ^[9] ; Achatz, Maria Isabel W. ^[10] ; Rosenberg, Carla ^[11] ; Krepischi, Ana C. V. ^[12]

Afiliação do(s) autor(es):Mostrar menos -

^[1] AC Camargo Canc Hosp. Int Ctr Res & Training

^[2] Hosp Clin Porto Alegre. Expt Res Ctr

^[3] Univ Sao Paulo. Inst Biosci

^[4] Portuguese Oncol Inst. Dept Genet

^[5] Portuguese Oncol Inst. Dept Genet

^[6] AC Camargo Canc Hosp. Int Ctr Res & Training

^[7] AC Camargo Canc Hosp. Int Ctr Res & Training

^[8] Portuguese Oncol Inst. Dept Genet

^[9] Hosp Clin Porto Alegre. Expt Res Ctr

^[10] AC Camargo Canc Hosp. Int Ctr Res & Training

^[11] Natl Inst Sci & Technol Oncogenom. Sao Paulo

^[12] AC Camargo Canc Hosp. Int Ctr Res & Training

• Tipo de documento: Artigo Científico
• Fonte: BMC CANCER; v. 12, JUN 12 2012.
• Citações Web of Science: 5

Resumo

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. (AU)

• Processo FAPESP: 08/57887-9 - Instituto Nacional de Oncogenômica
• Beneficiário: Luiz Paulo Kowalski
• Modalidade de apoio: Auxílio à Pesquisa - Temático