BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin

Autores
Solano, Angela Rosario; Aceto, Gitana Maria; Delettieres, Dreanina; Veschi, Serena; Neuman, Maria Isabel; Alonso, Eduardo; Chialina, Sergio; Chacón, Reinaldo Daniel; Renato, Mariani-Costantini; Podesta, Ernesto Jorge
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: The spectrum of BRCA1/2 genetic variation in breast-ovarian cancer patients has been scarcely investigated outside Europe and North America, with few reports for South America, where Amerindian founder effects and recent multiracial immigration are predicted to result in high genetic diversity. We describe here the results of BRCA1/BRCA2 germline analysis in an Argentinean series of breast/ovarian cancer patients selected for young age at diagnosis or breast/ovarian cancer family history. Methods: The study series (134 patients) included 37 cases diagnosed within 40 years of age and no family history (any ethnicity, fully-sequenced), and 97 cases with at least 2 affected relatives (any age), of which 57 were non-Ashkenazi (fully-sequenced) and 40 Ashkenazi (tested only for the founder mutations c.66_67delAG and c.5263insC in BRCA1 and c.5946delT in BRCA2). Discussion: We found 24 deleterious mutations (BRCA1:16; BRCA2: 8) in 38/134 (28.3%) patients, of which 6/37 (16.2%) within the young age group, 15/57 (26.3%) within the non-Ahkenazi positive for family history; and 17/40 (42.5%) within the Ashkenazi. Seven pathogenetic mutations were novel, five in BRCA1: c.1502_1505delAATT, c.2626_2627delAA c.2686delA, c.2728 C > T, c.3758_3759delCT, two in BRCA2: c.7105insA, c.793 + 1delG. We also detected 72 variants of which 54 previously reported and 17 novel, 33 detected in an individual patient. Four missense variants of unknown clinical significance, identified in 5 patients, are predicted to affect protein function. While global and European variants contributed near 45% of the detected BRCA1/2 variation, the significant fraction of new variants (25/96, 26%) suggests the presence of a South American genetic component. This study, the first conducted in Argentinean patients, highlights a significant impact of novel BRCA1/2 mutations and genetic variants, which may be regarded as putatively South American, and confirms the important role of founder BRCA1 and BRCA2 mutations in Argentinean Ashkenazi Jews. © 2012 Solano et al.
Fil: Solano, Angela Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Aceto, Gitana Maria. University Of G. D'annunzio Chieti And Pescara; Italia
Fil: Delettieres, Dreanina. Centro de Internación E Investigación Clínica; Argentina
Fil: Veschi, Serena. University Of G. D'annunzio Chieti And Pescara; Italia
Fil: Neuman, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Alonso, Eduardo. Hospital Italiano; Argentina
Fil: Chialina, Sergio. Hospital Italiano; Argentina
Fil: Chacón, Reinaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Renato, Mariani-Costantini. University Of G. D'annunzio Chieti And Pescara; Italia
Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Materia
Argentina
Ashkenazi
Brca1/Brca2
Early Onset Breast Cancer
Ethnicity
Familial Breast Cancer
Genetic Variants
Germline Mutations
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/67432
Acceder
id CONICETDig_3c8952d15fbd48ac634bfc90a44098bb
oai_identifier_str oai:ri.conicet.gov.ar:11336/67432
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American originSolano, Angela RosarioAceto, Gitana MariaDelettieres, DreaninaVeschi, SerenaNeuman, Maria IsabelAlonso, EduardoChialina, SergioChacón, Reinaldo DanielRenato, Mariani-CostantiniPodesta, Ernesto JorgeArgentinaAshkenaziBrca1/Brca2Early Onset Breast CancerEthnicityFamilial Breast CancerGenetic VariantsGermline Mutationshttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: The spectrum of BRCA1/2 genetic variation in breast-ovarian cancer patients has been scarcely investigated outside Europe and North America, with few reports for South America, where Amerindian founder effects and recent multiracial immigration are predicted to result in high genetic diversity. We describe here the results of BRCA1/BRCA2 germline analysis in an Argentinean series of breast/ovarian cancer patients selected for young age at diagnosis or breast/ovarian cancer family history. Methods: The study series (134 patients) included 37 cases diagnosed within 40 years of age and no family history (any ethnicity, fully-sequenced), and 97 cases with at least 2 affected relatives (any age), of which 57 were non-Ashkenazi (fully-sequenced) and 40 Ashkenazi (tested only for the founder mutations c.66_67delAG and c.5263insC in BRCA1 and c.5946delT in BRCA2). Discussion: We found 24 deleterious mutations (BRCA1:16; BRCA2: 8) in 38/134 (28.3%) patients, of which 6/37 (16.2%) within the young age group, 15/57 (26.3%) within the non-Ahkenazi positive for family history; and 17/40 (42.5%) within the Ashkenazi. Seven pathogenetic mutations were novel, five in BRCA1: c.1502_1505delAATT, c.2626_2627delAA c.2686delA, c.2728 C > T, c.3758_3759delCT, two in BRCA2: c.7105insA, c.793 + 1delG. We also detected 72 variants of which 54 previously reported and 17 novel, 33 detected in an individual patient. Four missense variants of unknown clinical significance, identified in 5 patients, are predicted to affect protein function. While global and European variants contributed near 45% of the detected BRCA1/2 variation, the significant fraction of new variants (25/96, 26%) suggests the presence of a South American genetic component. This study, the first conducted in Argentinean patients, highlights a significant impact of novel BRCA1/2 mutations and genetic variants, which may be regarded as putatively South American, and confirms the important role of founder BRCA1 and BRCA2 mutations in Argentinean Ashkenazi Jews. © 2012 Solano et al.Fil: Solano, Angela Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Aceto, Gitana Maria. University Of G. D'annunzio Chieti And Pescara; ItaliaFil: Delettieres, Dreanina. Centro de Internación E Investigación Clínica; ArgentinaFil: Veschi, Serena. University Of G. D'annunzio Chieti And Pescara; ItaliaFil: Neuman, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Alonso, Eduardo. Hospital Italiano; ArgentinaFil: Chialina, Sergio. Hospital Italiano; ArgentinaFil: Chacón, Reinaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Renato, Mariani-Costantini. University Of G. D'annunzio Chieti And Pescara; ItaliaFil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaSpringer2012-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67432Solano, Angela Rosario; Aceto, Gitana Maria; Delettieres, Dreanina; Veschi, Serena; Neuman, Maria Isabel; et al.; BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin; Springer; SpringerPlus; 1; 1; 9-2012; 1-102193-1801CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/2193-1801-1-20info:eu-repo/semantics/altIdentifier/url/https://springerplus.springeropen.com/articles/10.1186/2193-1801-1-20info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:19Zoai:ri.conicet.gov.ar:11336/67432instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:04:19.706CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin
title BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin
spellingShingle BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin
Solano, Angela Rosario
Argentina
Ashkenazi
Brca1/Brca2
Early Onset Breast Cancer
Ethnicity
Familial Breast Cancer
Genetic Variants
Germline Mutations
title_short BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin
title_full BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin
title_fullStr BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin
title_full_unstemmed BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin
title_sort BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin
dc.creator.none.fl_str_mv Solano, Angela Rosario
Aceto, Gitana Maria
Delettieres, Dreanina
Veschi, Serena
Neuman, Maria Isabel
Alonso, Eduardo
Chialina, Sergio
Chacón, Reinaldo Daniel
Renato, Mariani-Costantini
Podesta, Ernesto Jorge
author Solano, Angela Rosario
author_facet Solano, Angela Rosario
Aceto, Gitana Maria
Delettieres, Dreanina
Veschi, Serena
Neuman, Maria Isabel
Alonso, Eduardo
Chialina, Sergio
Chacón, Reinaldo Daniel
Renato, Mariani-Costantini
Podesta, Ernesto Jorge
author_role author
author2 Aceto, Gitana Maria
Delettieres, Dreanina
Veschi, Serena
Neuman, Maria Isabel
Alonso, Eduardo
Chialina, Sergio
Chacón, Reinaldo Daniel
Renato, Mariani-Costantini
Podesta, Ernesto Jorge
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Argentina
Ashkenazi
Brca1/Brca2
Early Onset Breast Cancer
Ethnicity
Familial Breast Cancer
Genetic Variants
Germline Mutations
topic Argentina
Ashkenazi
Brca1/Brca2
Early Onset Breast Cancer
Ethnicity
Familial Breast Cancer
Genetic Variants
Germline Mutations
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: The spectrum of BRCA1/2 genetic variation in breast-ovarian cancer patients has been scarcely investigated outside Europe and North America, with few reports for South America, where Amerindian founder effects and recent multiracial immigration are predicted to result in high genetic diversity. We describe here the results of BRCA1/BRCA2 germline analysis in an Argentinean series of breast/ovarian cancer patients selected for young age at diagnosis or breast/ovarian cancer family history. Methods: The study series (134 patients) included 37 cases diagnosed within 40 years of age and no family history (any ethnicity, fully-sequenced), and 97 cases with at least 2 affected relatives (any age), of which 57 were non-Ashkenazi (fully-sequenced) and 40 Ashkenazi (tested only for the founder mutations c.66_67delAG and c.5263insC in BRCA1 and c.5946delT in BRCA2). Discussion: We found 24 deleterious mutations (BRCA1:16; BRCA2: 8) in 38/134 (28.3%) patients, of which 6/37 (16.2%) within the young age group, 15/57 (26.3%) within the non-Ahkenazi positive for family history; and 17/40 (42.5%) within the Ashkenazi. Seven pathogenetic mutations were novel, five in BRCA1: c.1502_1505delAATT, c.2626_2627delAA c.2686delA, c.2728 C > T, c.3758_3759delCT, two in BRCA2: c.7105insA, c.793 + 1delG. We also detected 72 variants of which 54 previously reported and 17 novel, 33 detected in an individual patient. Four missense variants of unknown clinical significance, identified in 5 patients, are predicted to affect protein function. While global and European variants contributed near 45% of the detected BRCA1/2 variation, the significant fraction of new variants (25/96, 26%) suggests the presence of a South American genetic component. This study, the first conducted in Argentinean patients, highlights a significant impact of novel BRCA1/2 mutations and genetic variants, which may be regarded as putatively South American, and confirms the important role of founder BRCA1 and BRCA2 mutations in Argentinean Ashkenazi Jews. © 2012 Solano et al.
Fil: Solano, Angela Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Aceto, Gitana Maria. University Of G. D'annunzio Chieti And Pescara; Italia
Fil: Delettieres, Dreanina. Centro de Internación E Investigación Clínica; Argentina
Fil: Veschi, Serena. University Of G. D'annunzio Chieti And Pescara; Italia
Fil: Neuman, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Alonso, Eduardo. Hospital Italiano; Argentina
Fil: Chialina, Sergio. Hospital Italiano; Argentina
Fil: Chacón, Reinaldo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
Fil: Renato, Mariani-Costantini. University Of G. D'annunzio Chieti And Pescara; Italia
Fil: Podesta, Ernesto Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina
description Background: The spectrum of BRCA1/2 genetic variation in breast-ovarian cancer patients has been scarcely investigated outside Europe and North America, with few reports for South America, where Amerindian founder effects and recent multiracial immigration are predicted to result in high genetic diversity. We describe here the results of BRCA1/BRCA2 germline analysis in an Argentinean series of breast/ovarian cancer patients selected for young age at diagnosis or breast/ovarian cancer family history. Methods: The study series (134 patients) included 37 cases diagnosed within 40 years of age and no family history (any ethnicity, fully-sequenced), and 97 cases with at least 2 affected relatives (any age), of which 57 were non-Ashkenazi (fully-sequenced) and 40 Ashkenazi (tested only for the founder mutations c.66_67delAG and c.5263insC in BRCA1 and c.5946delT in BRCA2). Discussion: We found 24 deleterious mutations (BRCA1:16; BRCA2: 8) in 38/134 (28.3%) patients, of which 6/37 (16.2%) within the young age group, 15/57 (26.3%) within the non-Ahkenazi positive for family history; and 17/40 (42.5%) within the Ashkenazi. Seven pathogenetic mutations were novel, five in BRCA1: c.1502_1505delAATT, c.2626_2627delAA c.2686delA, c.2728 C > T, c.3758_3759delCT, two in BRCA2: c.7105insA, c.793 + 1delG. We also detected 72 variants of which 54 previously reported and 17 novel, 33 detected in an individual patient. Four missense variants of unknown clinical significance, identified in 5 patients, are predicted to affect protein function. While global and European variants contributed near 45% of the detected BRCA1/2 variation, the significant fraction of new variants (25/96, 26%) suggests the presence of a South American genetic component. This study, the first conducted in Argentinean patients, highlights a significant impact of novel BRCA1/2 mutations and genetic variants, which may be regarded as putatively South American, and confirms the important role of founder BRCA1 and BRCA2 mutations in Argentinean Ashkenazi Jews. © 2012 Solano et al.
publishDate 2012
dc.date.none.fl_str_mv 2012-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/67432
Solano, Angela Rosario; Aceto, Gitana Maria; Delettieres, Dreanina; Veschi, Serena; Neuman, Maria Isabel; et al.; BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin; Springer; SpringerPlus; 1; 1; 9-2012; 1-10
2193-1801
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67432
identifier_str_mv Solano, Angela Rosario; Aceto, Gitana Maria; Delettieres, Dreanina; Veschi, Serena; Neuman, Maria Isabel; et al.; BRCA1 and BRCA2 analysis of argentinean breast/ovarian cancer patients selected for age and family history highlights a role for novel mutations of putative south-American origin; Springer; SpringerPlus; 1; 1; 9-2012; 1-10
2193-1801
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/https://springerplus.springeropen.com/articles/10.1186/2193-1801-1-20
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eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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