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Mutation screening of TP53, CHEK2 and BRCA genes in patients at high risk for hereditary breast and ovarian cancer (HBOC) in Brazil

Breast Cancer volume 26, pages 397–405 (2019)Cite this article

Abstract

Background

Few studies related to hereditary breast and ovarian cancer syndrome (HBOC) have been conducted in Brazil, and they are restricted to only small areas of the country. Here, we report the mutation profile of BRCA1/2, CHEK2 and TP53 genes in a cohort from Minas Gerais state.

Methods

These genes from 44 patients at high risk for HBOC were screened through high-resolution melting and/or sequencing. The pathogenicity of the alterations was checked using ClinVar database and bioinformatics programs.

Results

In BRCA genes we identified 46 variants, 38 without clinical significance and 8 pathogenic mutations including a new pathogenic mutation in BRCA1 gene (c.4688_4694delACCTGGAinsG). The most prevalent pathogenic mutation was c.4829_4830delTG, in the BRCA2 gene. This mutation was not described in the Brazilian population up to now and in this study, it was described with a prevalence of 6.8%. The p.R337H mutation in TP53 gene was found in one patient clinically diagnosed as HBOC and without clinical criteria for Li-Fraumeni syndrome. In CHEK2 gene, the undescribed variant c.485A > G was found and it presents as probably pathogenic through in silico analyses. Pathogenic mutations were found in 29.5% of the patients, 11.3% in BRCA1, 15.9% in BRCA2 and 2.3% in TP53 gene.

Conclusions

Brazilian population is one of the most heterogeneous in the world and the mutational profile knowledge of genes related to HBOC from different regions can contribute to the definition of more cost-effective strategies for the prevention, identification and treatment of cancer.

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Funding

Associação do Combate ao Câncer do Centro-Oeste de Minas (ACCCOM), Fundação de Amparo à Pesquisa do estado de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

Author information

Affiliations

  1. Universidade Federal de São João del Rei (UFSJ), 400 Sebastião Gonçalves Coelho Ave., Chanadour, Divinópolis, MG, 35501-296, Brazil

    Nilson Moreira Cipriano Jr, Amanda Marques de Brito, Eneida Santos de Oliveira, Débora de Oliveira Lopes & Luciana Lara dos Santos

  2. Associação de Combate ao Câncer do Centro Oeste de Minas Gerais (ACCCOM), 500 Topázio st., Niterói, Divinópolis, MG, 35500-215, Brazil

    Fabiana Castro de Faria, Sara Lemos & Angélica Nogueira Rodrigues

  3. Faculdade de Medicina, Universidade Federal de Minas Gerais (UFMG), 190 Professor Alfredo Balena Ave., Santa Efigênia, Belo Horizonte, MG, 30160-011, Brazil

    Angélica Nogueira Rodrigues

  4. Grupo Brasileiro de Tumores Ginecológicos (EVA), São Paulo, Brazil

    Angélica Nogueira Rodrigues

Authors
  1. Nilson Moreira Cipriano Jr
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  2. Amanda Marques de Brito
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  3. Eneida Santos de Oliveira
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  4. Fabiana Castro de Faria
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  5. Sara Lemos
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  6. Angélica Nogueira Rodrigues
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  7. Débora de Oliveira Lopes
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  8. Luciana Lara dos Santos
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Corresponding author

Correspondence to Luciana Lara dos Santos.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Cipriano, N.M., de Brito, A.M., de Oliveira, E.S. et al. Mutation screening of TP53, CHEK2 and BRCA genes in patients at high risk for hereditary breast and ovarian cancer (HBOC) in Brazil. Breast Cancer 26, 397–405 (2019). https://doi.org/10.1007/s12282-018-00938-z

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  • DOI: https://doi.org/10.1007/s12282-018-00938-z

Keywords

  • HBOC
  • BRCA
  • CHEK2
  • TP53
  • Brazil