Evaluation of genomic copy number variation of genes that predispose patients with...
| Full text | |
| Author(s): Show less - |
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
|
| Affiliation: Show less - | [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 |
| Abstract | |
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 |