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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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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Autor(es):
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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]
Número total de Autores: 17
Afiliação do(s) autor(es):
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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
Número total de Afiliações: 12
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