Comprehensive Analysis of BRCA1, BRCA2 and TP53 Germline Mutation and Tumor Characterization: A Portrait of Early-Onset Breast Cancer in Brazil

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Carraro, Dirce Maria ^{[1, 2]} ; Azevedo Koike Folgueira, Maria Aparecida ^[3] ; Garcia Lisboa, Bianca Cristina ^[1] ; Ribeiro Olivieri, Eloisa Helena ^[1] ; Vitorino Krepischi, Ana Cristina ^{[2, 4]} ; de Carvalho, Alex Fiorini ^[1] ; de Carvalho Mota, Louise Danielle ^[1] ; Puga, Renato David ^[5] ; Maciel, Maria do Socorro ^[6] ; Depieri Michelli, Rodrigo Augusto ^[7] ; de Lyra, Eduardo Carneiro ^[8] ; Giorgi Grosso, Stana Helena ; Soares, Fernando Augusto ^[9] ; de Souza Waddington Achatz, Maria Isabel Alves ^{[10, 2]} ; Brentani, Helena ^[11] ; Moreira-Filho, Carlos Alberto ^[12] ; Brentani, Maria Mitzi ^[3]

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^[1] AC Camargo Hosp, Lab Genom & Mol Biol, Sao Paulo - Brazil

^[2] Natl Inst Sci & Technol Oncogenom INCITO, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Radiol & Oncol Dept, Sao Paulo - Brazil

^[4] AC Camargo Hosp, Lab Struct Genom, Sao Paulo - Brazil

^[5] AC Camargo Hosp, Lab Bioinformat & Bioestat, Sao Paulo - Brazil

^[6] AC Camargo Hosp, Dept Mastol, Sao Paulo - Brazil

^[7] Hosp Canc Barretos, Dept Oncogenet, Sao Paulo - Brazil

^[8] IBCC, Dept Mastol, Sao Paulo - Brazil

^[9] AC Camargo Hosp, Dept Invest Pathol, Sao Paulo - Brazil

^[10] AC Camargo Hosp, Dept Mol Oncogenet, Sao Paulo - Brazil

^[11] Univ Sao Paulo, Fac Med, Dept Psychiat, Sao Paulo - Brazil

^[12] Univ Sao Paulo, Fac Med, Dept Pediat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 3 MAR 1 2013.
• Citações Web of Science: 40

Resumo

Germline mutations in BRCA1, BRCA2 and TP53 genes have been identified as one of the most important disease-causing issues in young breast cancer patients worldwide. The specific defective biological processes that trigger germline mutation-associated and -negative tumors remain unclear. To delineate an initial portrait of Brazilian early-onset breast cancer, we performed an investigation combining both germline and tumor analysis. Germline screening of the BRCA1, BRCA2, CHEK2 (c.1100delC) and TP53 genes was performed in 54 unrelated patients <35 y; their tumors were investigated with respect to transcriptional and genomic profiles as well as hormonal receptors and HER2 expression/amplification. Germline mutations were detected in 12 out of 54 patients (22%) {[}7 in BRCA1 (13%), 4 in BRCA2 (7%) and one in TP53 (2%) gene]. A cancer familial history was present in 31.4% of the unrelated patients, from them 43.7% were carriers for germline mutation (37.5% in BRCA1 and in 6.2% in the BRCA2 genes). Fifty percent of the unrelated patients with hormone receptor-negative tumors carried BRCA1 mutations, percentage increasing to 83% in cases with familial history of cancer. Over-representation of DNA damage-, cellular and cell cycle-related processes was detected in the up-regulated genes of BRCA1/2-associated tumors, whereas cell and embryo development-related processes were over-represented in the up-regulated genes of BRCA1/2-negative tumors, suggesting distinct mechanisms driving the tumorigenesis. An initial portrait of the early-onset breast cancer patients in Brazil was generated pointing out that hormone receptor-negative tumors and positive familial history are two major risk factors for detection of a BRCA1 germline mutation. Additionally, the data revealed molecular factors that potentially trigger the tumor development in young patients. (AU)

• Processo FAPESP: 08/57887-9 - Instituto Nacional de Oncogenômica
• Beneficiário: Luiz Paulo Kowalski
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/10088-7 - Expressão gênica de fibroblastos associados a carcinomas de mama classificados em subtipos de acordo com receptores de estrógeno e progesterona e C-ERBB2
• Beneficiário: Maria Mitzi Brentani
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 98/14335-2 - Antonio Prudente Cancer Research Center
• Beneficiário: Fernando Augusto Soares
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs