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Screening and characterization of BRCA2 c.156_157insAlu in Brazil: Results from 1380 individuals from the South and Southeast

  • Author Footnotes
    1 Both authors contributed equally to this work.
    Paula Silva Felicio
    Footnotes
    1 Both authors contributed equally to this work.
    Affiliations
    Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil
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  • Author Footnotes
    1 Both authors contributed equally to this work.
    Barbara Alemar
    Footnotes
    1 Both authors contributed equally to this work.
    Affiliations
    Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul. Av. Bento Gonçalves, 9500 – Prédio 43323M. Porto Alegre 91501-970, Rio Grande do Sul, Brazil

    Laboratório de Medicina Genômica—Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350. Porto Alegre 90035-903, Rio Grande do Sul, Brazil
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  • Aline Silva Coelho
    Affiliations
    Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil
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  • Gustavo Noriz Berardinelli
    Affiliations
    Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil
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  • Matias Eliseo Melendez
    Affiliations
    Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil
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  • André Van Helvoort Lengert
    Affiliations
    Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil
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  • Rodrigo Depieri Miche lli
    Affiliations
    Department of Oncogenetics, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil
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  • Rui M. Reis
    Affiliations
    Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil

    Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus de Gualtar, Braga 4710-057, Portugal

    ICVS/3B's—PT Government Associate Laboratory, Braga/Guimarães, Portugal
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  • Gabriela Carvalho Fernandes
    Affiliations
    Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil
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  • Ingrid Petroni Ewald
    Affiliations
    Santa Casa de Misericórdia de Porto Alegre. Av. Independência, 75. Porto Alegre 90035-072, Rio Grande do Sul, Brazil
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  • Camila Matzenbacher Bittar
    Affiliations
    Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul. Av. Bento Gonçalves, 9500 – Prédio 43323M. Porto Alegre 91501-970, Rio Grande do Sul, Brazil

    Laboratório de Medicina Genômica—Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350. Porto Alegre 90035-903, Rio Grande do Sul, Brazil
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  • Cristina Brinckmann Oliveira Netto
    Affiliations
    Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre. Rua Ramiro Barcelos, 2350. Porto Alegre 90035-903, Rio Grande do Sul, Brazil
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  • Osvaldo Artigalas
    Affiliations
    Hospital Moinhos de Vento, Rua Ramiro Barcelos, 910. Porto Alegre 91790-560, Rio Grande do Sul, Brazil
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  • Ana Peixoto
    Affiliations
    Department of Genetics, Portuguese Oncology Institute, R. Dr António Bernardino de Almeida. Porto 4200-072, Portugal
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  • Manuela Pinheiro
    Affiliations
    Department of Genetics, Portuguese Oncology Institute, R. Dr António Bernardino de Almeida. Porto 4200-072, Portugal
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  • Manuel R. Teixeira
    Affiliations
    Department of Genetics, Portuguese Oncology Institute, R. Dr António Bernardino de Almeida. Porto 4200-072, Portugal

    Biomedical Sciences Institute Abel Salazar (ICBAS), University of Porto, R. Jorge de Viterbo Ferreira, 228, Porto 4050-313, Portugal
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  • Fernando Regla Vargas
    Affiliations
    Laboratório de Epidemiologia de Malformações Congênitas, Instituto Oswaldo Cruz (FIOCRUZ), Brazil

    Universidade Federal do Estado do Rio de Janeiro, Brazil
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  • Anna Cláudia Evangelista dos Santos
    Affiliations
    Genetics Program, Instituto Nacional de Câncer, Rua André Cavalcanti, 37. Rio de Janeiro 20231-050, Rio de Janeiro, Brazil
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  • Miguel Angelo Martins Moreira
    Affiliations
    Genetics Program, Instituto Nacional de Câncer, Rua André Cavalcanti, 37. Rio de Janeiro 20231-050, Rio de Janeiro, Brazil
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  • Author Footnotes
    2 Both authors jointly supervised this work.
    Patricia Ashton-Prolla
    Correspondence
    Corresponding author. Present address: Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre. Rua Ramiro Barcelos, 2350. Porto Alegre 90035-903, Rio Grande do Sul, Brazil. Email: [email protected]
    Footnotes
    2 Both authors jointly supervised this work.
    Affiliations
    Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul. Av. Bento Gonçalves, 9500 – Prédio 43323M. Porto Alegre 91501-970, Rio Grande do Sul, Brazil

    Laboratório de Medicina Genômica—Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350. Porto Alegre 90035-903, Rio Grande do Sul, Brazil

    Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre. Rua Ramiro Barcelos, 2350. Porto Alegre 90035-903, Rio Grande do Sul, Brazil
    Search for articles by this author
  • Author Footnotes
    2 Both authors jointly supervised this work.
    Edenir Inêz Palmero
    Correspondence
    Corresponding author at: Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Avenida Antenor Duarte Vilela, 1331, Barretos 14784-400, São Paulo, Brazil. Email: [email protected]
    Footnotes
    2 Both authors jointly supervised this work.
    Affiliations
    Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331. Barretos 14784-400, São Paulo, Brazil

    Barretos School of Health Science, Dr. Paulo Prata. Av. Loja Maçonica Renovadora, 68. Barretos 14785-002, São Paulo, Brazil
    Search for articles by this author
  • Author Footnotes
    1 Both authors contributed equally to this work.
    2 Both authors jointly supervised this work.

      Highlights

      • In our cohort, the frequency of the Portuguese BRCA2 founder mutation (c.156_157insAlu) was 0.65%.
      • The most frequent ancestry proportions of the mutation carriers were European and African.
      • 67% of the families presented a pattern compatible with the Portuguese ancestral haplotype.

      Abstract

      Portuguese immigration to Brazil occurred in several waves and greatly contributed to the genetic composition of current Brazilian population. In this study, we evaluated the frequency of a Portuguese founder Alu insertion in BRCA2 exon 3 (c.156_157insAlu) among individuals fulfilling Hereditary Breast and Ovarian Cancer (HBOC) syndrome criteria in 1,380 unrelated families originated from three distinct Brazilian States. We identified the c.156_157insAlu BRCA2 mutation in nine (9/1,380; 0.65%) probands analised. In carrier probands, European ancestry had the highest proportion (80%), followed by the African (10%) and Amerindian and in most families with the rearrangement, haplotype analyses were compatible with the Portuguese ancestral haplotype. In conclusion, the present study reports a low albeit relevant frequency of the Portuguese BRCA2 founder mutation c.156_157insAlu in Brazilian patients at-risk for HBOC Brazilian population.

      Keywords

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