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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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]
Total Authors: 17
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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
Total Affiliations: 12
Document type: Journal article
Source: PLoS One; v. 8, n. 3 MAR 1 2013.
Web of Science Citations: 40

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)

FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
Grantee:Luiz Paulo Kowalski
Support type: Research Projects - Thematic Grants
FAPESP's process: 09/10088-7 - Gene expression profiling of the tumor fibroblasts in breast cancer classified into subtypes by estrogen and progestorone receptors and ERBB-2 status
Grantee:Maria Mitzi Brentani
Support type: Research Projects - Thematic Grants
FAPESP's process: 98/14335-2 - Antonio Prudente Cancer Research Center
Grantee:Fernando Augusto Soares
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC