BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome
Abstract Approximately 5-10% of breast cancers are caused by germline mutations in high penetrance predisposition genes. Among these, BRCA1 and BRCA2, which are associated with the Hereditary Breast and Ovarian Cancer (HBOC) syndrome, are the most frequently affected genes. Recent studies confirm that gene rearrangements, especially in BRCA1, are responsible for a significant proportion of mutations in certain populations. In this study we determined the prevalence of BRCA rearrangements in 145 unrelated Brazilian individuals at risk for HBOC syndrome who had not been previously tested for BRCA mutations. Using Multiplex Ligation-dependent Probe Amplification (MLPA) and a specific PCR-based protocol to identify a Portuguese founder BRCA2 mutation, we identified two (1,4%) individuals with germline BRCA1 rearrangements (c.547+240_5193+178del and c.4675+467_5075-990del) and three probands with the c.156_157insAlu founder BRCA2 rearrangement. Furthermore, two families with false positive MLPA results were shown to carry a deleterious point mutation at the probe binding site. This study comprises the largest Brazilian series of HBOC families tested for BRCA1 and BRCA2 rearrangements to date and includes patients from three regions of the country. The overall observed rearrangement frequency of 3.44% indicates that rearrangements are relatively uncommon in the admixed population of Brazil.
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Sociedade Brasileira de Genética
2016
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oai:scielo:S1415-475720160002002232017-03-17BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer SyndromeEwald,Ingrid PetroniCossio,Silvia LilianaPalmero,Edenir InezPinheiro,ManuelaNascimento,Ivana Lucia de OliveiraMachado,Taisa Manuela BonfimSandes,Kiyoko AbeToralles,BetâniaGaricochea,BernardoIzetti,PatriciaPereira,Maria Luiza SaraivaBock,HugoVargas,Fernando ReglaMoreira,Miguel Ângelo MartinsPeixoto,AnaTeixeira,Manuel R.Ashton-Prolla,Patricia Breast cancer Hereditary Breast and Ovarian Cancer syndrome gene rearrangements BRCA gene Abstract Approximately 5-10% of breast cancers are caused by germline mutations in high penetrance predisposition genes. Among these, BRCA1 and BRCA2, which are associated with the Hereditary Breast and Ovarian Cancer (HBOC) syndrome, are the most frequently affected genes. Recent studies confirm that gene rearrangements, especially in BRCA1, are responsible for a significant proportion of mutations in certain populations. In this study we determined the prevalence of BRCA rearrangements in 145 unrelated Brazilian individuals at risk for HBOC syndrome who had not been previously tested for BRCA mutations. Using Multiplex Ligation-dependent Probe Amplification (MLPA) and a specific PCR-based protocol to identify a Portuguese founder BRCA2 mutation, we identified two (1,4%) individuals with germline BRCA1 rearrangements (c.547+240_5193+178del and c.4675+467_5075-990del) and three probands with the c.156_157insAlu founder BRCA2 rearrangement. Furthermore, two families with false positive MLPA results were shown to carry a deleterious point mutation at the probe binding site. This study comprises the largest Brazilian series of HBOC families tested for BRCA1 and BRCA2 rearrangements to date and includes patients from three regions of the country. The overall observed rearrangement frequency of 3.44% indicates that rearrangements are relatively uncommon in the admixed population of Brazil.info:eu-repo/semantics/openAccessSociedade Brasileira de GenéticaGenetics and Molecular Biology v.39 n.2 20162016-06-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572016000200223en10.1590/1678-4685-gmb-2014-0350 |
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Ewald,Ingrid Petroni Cossio,Silvia Liliana Palmero,Edenir Inez Pinheiro,Manuela Nascimento,Ivana Lucia de Oliveira Machado,Taisa Manuela Bonfim Sandes,Kiyoko Abe Toralles,Betânia Garicochea,Bernardo Izetti,Patricia Pereira,Maria Luiza Saraiva Bock,Hugo Vargas,Fernando Regla Moreira,Miguel Ângelo Martins Peixoto,Ana Teixeira,Manuel R. Ashton-Prolla,Patricia |
spellingShingle |
Ewald,Ingrid Petroni Cossio,Silvia Liliana Palmero,Edenir Inez Pinheiro,Manuela Nascimento,Ivana Lucia de Oliveira Machado,Taisa Manuela Bonfim Sandes,Kiyoko Abe Toralles,Betânia Garicochea,Bernardo Izetti,Patricia Pereira,Maria Luiza Saraiva Bock,Hugo Vargas,Fernando Regla Moreira,Miguel Ângelo Martins Peixoto,Ana Teixeira,Manuel R. Ashton-Prolla,Patricia BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome |
author_facet |
Ewald,Ingrid Petroni Cossio,Silvia Liliana Palmero,Edenir Inez Pinheiro,Manuela Nascimento,Ivana Lucia de Oliveira Machado,Taisa Manuela Bonfim Sandes,Kiyoko Abe Toralles,Betânia Garicochea,Bernardo Izetti,Patricia Pereira,Maria Luiza Saraiva Bock,Hugo Vargas,Fernando Regla Moreira,Miguel Ângelo Martins Peixoto,Ana Teixeira,Manuel R. Ashton-Prolla,Patricia |
author_sort |
Ewald,Ingrid Petroni |
title |
BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome |
title_short |
BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome |
title_full |
BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome |
title_fullStr |
BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome |
title_full_unstemmed |
BRCA1 and BRCA2 rearrangements in Brazilian individuals with Hereditary Breast and Ovarian Cancer Syndrome |
title_sort |
brca1 and brca2 rearrangements in brazilian individuals with hereditary breast and ovarian cancer syndrome |
description |
Abstract Approximately 5-10% of breast cancers are caused by germline mutations in high penetrance predisposition genes. Among these, BRCA1 and BRCA2, which are associated with the Hereditary Breast and Ovarian Cancer (HBOC) syndrome, are the most frequently affected genes. Recent studies confirm that gene rearrangements, especially in BRCA1, are responsible for a significant proportion of mutations in certain populations. In this study we determined the prevalence of BRCA rearrangements in 145 unrelated Brazilian individuals at risk for HBOC syndrome who had not been previously tested for BRCA mutations. Using Multiplex Ligation-dependent Probe Amplification (MLPA) and a specific PCR-based protocol to identify a Portuguese founder BRCA2 mutation, we identified two (1,4%) individuals with germline BRCA1 rearrangements (c.547+240_5193+178del and c.4675+467_5075-990del) and three probands with the c.156_157insAlu founder BRCA2 rearrangement. Furthermore, two families with false positive MLPA results were shown to carry a deleterious point mutation at the probe binding site. This study comprises the largest Brazilian series of HBOC families tested for BRCA1 and BRCA2 rearrangements to date and includes patients from three regions of the country. The overall observed rearrangement frequency of 3.44% indicates that rearrangements are relatively uncommon in the admixed population of Brazil. |
publisher |
Sociedade Brasileira de Genética |
publishDate |
2016 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572016000200223 |
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