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Sci Rep. 2018 Jun 15;8(1):9188. doi: 10.1038/s41598-018-27315-2.

The germline mutational landscape of BRCA1 and BRCA2 in Brazil.

Author information

1
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil.
2
Barretos School of Health Science, Faculdade de Ciências da Saúde de Barretos Dr. Paulo Prata, Barretos, Brazil.
3
International Research Center/CIPE, AC Camargo Cancer Center, Sao Paulo, Brazil.
4
Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
5
Laboratório de Medicina Genômica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
6
Programa de Genética, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
7
Laboratório de Genética Humana e Médica, Programa de Pós-graduação em Genética e Biologia Molecular - Universidade Federal do Pará, Belém do Pará, Brazil.
8
Núcleo de Pesquisas em Oncologia, Programa de Pós-graduação em Genética e Biologia Molecular - Universidade Federal do Pará, Belém do Pará, Brazil.
9
Laboratório de Imunologia e Biologia Molecular, Universidade Federal da Bahia, Salvador, Brazil.
10
Department of Oncogenetics, Barretos Cancer Hospital, Barretos, Brazil.
11
Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal.
12
ICVS/3B's-PT Government Associate Laboratory, Braga, Guimarães, Portugal.
13
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics - Department of Health and Human Services/Centro de Oncologia, NCI-NIH/Hospital Sírio Libanês, Bethesda, USA.
14
Oncogenetics and Clinical Oncology Departments, AC Camargo Cancer Center, São Paulo, Brazil.
15
Breast Surgery Department, AC Camargo Cancer Center, São Paulo, Brazil.
16
Birth Defects Epidemiology Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
17
Genetics and Molecular Biology Department, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
18
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
19
Laboratório de Biologia Molecular, Hospital Ophir Loyola, Belem do Pará, Brazil.
20
Núcleo de Oncologia da Bahia - Grupo Oncoclínicas, Salvador, Brazil.
21
Centro de Paulista de Oncologia, Oncoclínicas, São Paulo, Brazil.
22
Departamento de Oncologia Clínica, Hospital Israelita Albert Einstein, São Paulo, Brazil.
23
COAEM - Centro Oncológico Antonio Ermirio de Moraes, São Paulo, Brazil.
24
Centro de Aconselhamento Genético, Hospital Israelita Albert Einstein, São Paulo, Brazil.
25
Rede Mater Dei de Saúde, Belo Horizonte, Brazil.
26
Instituto Hermes Pardini, Belo Horizonte, Brazil.
27
Oncopraxis, Rio de Janeiro, Brazil.
28
Hospital Moinhos de Vento (HMV), Porto Alegre, Brazil.
29
Departamento de Radiologia e Oncologia, Instituto do Câncer do Estado de São Paulo/Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
30
Departamento de Biologia Celular e Genética - Serviço de Aconselhamento Genético, Centro de Oncologia Avançado/CECAN, Universidade Federal do Rio Grande do Norte - Hospital Liga Contra o Câncer, Natal, Brazil.
31
Rede D'Or (Fujiday and OncoStar), Fortaleza, Brazil.
32
Oncocentro, Hospital São Carlos, Fortaleza, Brazil.
33
CLION, CAM Group, Salvador, Brazil.
34
Laboratório Genoma, Vitória, Brazil.
35
Serviço de Genética Médica do Hospital Universitário, Divisão de Clínica Médica, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
36
Hospital Universitário Professor Edgard Santos, Serviço de Genética Médica, Universidade Federal da Bahia, Salvador, Brazil.
37
Departamento de Oncogenética, Oncoclin de Manaus, Manaus, Brazil.
38
Department of Population Sciences, Division of Clinical Cancer Genomics - City of Hope, Duarte, USA.
39
Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. pprolla@gmail.com.
40
Laboratório de Medicina Genômica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. pprolla@gmail.com.
41
Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. pprolla@gmail.com.

Abstract

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.

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