BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population

Autores
Cardozo, Florencia C.; Goncalves, Susana; Mele, Pablo Gustavo; Liria, Natalia C.; Sganga, Leonardo; Diaz Perez, Ignacio; Podesta, Ernesto Jorge; Podesta, Ernesto Jorge
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients. The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population. Results: A total of 96 patients carried a pathogenic germline mutation, accounting for an overall 24.1% mutation incidence. Among mutation carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient exhibited a mutation in both genes. Three pathogenic mutations were recurrent mutations detected five, three, and four times and represented 12.5% of the mutated samples. Worth highlighting, a 50% mutation incidence was detected when breast and ovarian cancer coexisted in the same patient. Novel mutations amounted to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational spectrum compared to our previously published data on breast cancer patients. Conclusions: In sum, our study provides novel data on ovarian BRCA1/2 mutation prevalence worldwide, enhances adequate patient selection for family counseling and prevention, and sheds light on the benefits of iPARP treatment.
Fil: Cardozo, Florencia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina
Fil: Goncalves, Susana. AstraZeneca Argentina MC; Argentina
Fil: Mele, Pablo Gustavo. 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: Liria, Natalia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina
Fil: Sganga, Leonardo. AstraZeneca Argentina MC; Argentina
Fil: Diaz Perez, Ignacio. AstraZeneca Argentina MC; Argentina
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
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. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina
Materia
BRCA1/2 AND OVARIAN CANCER
IPARP TREATMENT
OVARIAN CANCER
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/86770
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/86770
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar populationCardozo, Florencia C.Goncalves, SusanaMele, Pablo GustavoLiria, Natalia C.Sganga, LeonardoDiaz Perez, IgnacioPodesta, Ernesto JorgePodesta, Ernesto JorgeBRCA1/2 AND OVARIAN CANCERIPARP TREATMENTOVARIAN CANCERhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Background: Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients. The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population. Results: A total of 96 patients carried a pathogenic germline mutation, accounting for an overall 24.1% mutation incidence. Among mutation carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient exhibited a mutation in both genes. Three pathogenic mutations were recurrent mutations detected five, three, and four times and represented 12.5% of the mutated samples. Worth highlighting, a 50% mutation incidence was detected when breast and ovarian cancer coexisted in the same patient. Novel mutations amounted to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational spectrum compared to our previously published data on breast cancer patients. Conclusions: In sum, our study provides novel data on ovarian BRCA1/2 mutation prevalence worldwide, enhances adequate patient selection for family counseling and prevention, and sheds light on the benefits of iPARP treatment.Fil: Cardozo, Florencia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Goncalves, Susana. AstraZeneca Argentina MC; ArgentinaFil: Mele, Pablo Gustavo. 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: Liria, Natalia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaFil: Sganga, Leonardo. AstraZeneca Argentina MC; ArgentinaFil: Diaz Perez, Ignacio. AstraZeneca Argentina MC; ArgentinaFil: 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; ArgentinaFil: 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. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; ArgentinaBioMed Central2018-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/86770Cardozo, Florencia C.; Goncalves, Susana; Mele, Pablo Gustavo; Liria, Natalia C.; Sganga, Leonardo; et al.; BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population; BioMed Central; Human Genomics; 12; 39; 1-2018; 1-81479-7364CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/s40246-018-0171-5info:eu-repo/semantics/altIdentifier/url/https://humgenomics.biomedcentral.com/articles/10.1186/s40246-018-0171-5info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:57:13Zoai:ri.conicet.gov.ar:11336/86770instacron: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:34982025-10-22 11:57:14.059CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population
title BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population
spellingShingle BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population
Cardozo, Florencia C.
BRCA1/2 AND OVARIAN CANCER
IPARP TREATMENT
OVARIAN CANCER
title_short BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population
title_full BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population
title_fullStr BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population
title_full_unstemmed BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population
title_sort BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population
dc.creator.none.fl_str_mv Cardozo, Florencia C.
Goncalves, Susana
Mele, Pablo Gustavo
Liria, Natalia C.
Sganga, Leonardo
Diaz Perez, Ignacio
Podesta, Ernesto Jorge
Podesta, Ernesto Jorge
author Cardozo, Florencia C.
author_facet Cardozo, Florencia C.
Goncalves, Susana
Mele, Pablo Gustavo
Liria, Natalia C.
Sganga, Leonardo
Diaz Perez, Ignacio
Podesta, Ernesto Jorge
author_role author
author2 Goncalves, Susana
Mele, Pablo Gustavo
Liria, Natalia C.
Sganga, Leonardo
Diaz Perez, Ignacio
Podesta, Ernesto Jorge
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv BRCA1/2 AND OVARIAN CANCER
IPARP TREATMENT
OVARIAN CANCER
topic BRCA1/2 AND OVARIAN CANCER
IPARP TREATMENT
OVARIAN CANCER
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: Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients. The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population. Results: A total of 96 patients carried a pathogenic germline mutation, accounting for an overall 24.1% mutation incidence. Among mutation carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient exhibited a mutation in both genes. Three pathogenic mutations were recurrent mutations detected five, three, and four times and represented 12.5% of the mutated samples. Worth highlighting, a 50% mutation incidence was detected when breast and ovarian cancer coexisted in the same patient. Novel mutations amounted to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational spectrum compared to our previously published data on breast cancer patients. Conclusions: In sum, our study provides novel data on ovarian BRCA1/2 mutation prevalence worldwide, enhances adequate patient selection for family counseling and prevention, and sheds light on the benefits of iPARP treatment.
Fil: Cardozo, Florencia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina
Fil: Goncalves, Susana. AstraZeneca Argentina MC; Argentina
Fil: Mele, Pablo Gustavo. 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: Liria, Natalia C.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina
Fil: Sganga, Leonardo. AstraZeneca Argentina MC; Argentina
Fil: Diaz Perez, Ignacio. AstraZeneca Argentina MC; Argentina
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
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. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina
description Background: Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients. The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population. Results: A total of 96 patients carried a pathogenic germline mutation, accounting for an overall 24.1% mutation incidence. Among mutation carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient exhibited a mutation in both genes. Three pathogenic mutations were recurrent mutations detected five, three, and four times and represented 12.5% of the mutated samples. Worth highlighting, a 50% mutation incidence was detected when breast and ovarian cancer coexisted in the same patient. Novel mutations amounted to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational spectrum compared to our previously published data on breast cancer patients. Conclusions: In sum, our study provides novel data on ovarian BRCA1/2 mutation prevalence worldwide, enhances adequate patient selection for family counseling and prevention, and sheds light on the benefits of iPARP treatment.
publishDate 2018
dc.date.none.fl_str_mv 2018-01
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/11336/86770
Cardozo, Florencia C.; Goncalves, Susana; Mele, Pablo Gustavo; Liria, Natalia C.; Sganga, Leonardo; et al.; BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population; BioMed Central; Human Genomics; 12; 39; 1-2018; 1-8
1479-7364
CONICET Digital
CONICET
url http://hdl.handle.net/11336/86770
identifier_str_mv Cardozo, Florencia C.; Goncalves, Susana; Mele, Pablo Gustavo; Liria, Natalia C.; Sganga, Leonardo; et al.; BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer patients: Comparison with breast cancer variants in a similar population; BioMed Central; Human Genomics; 12; 39; 1-2018; 1-8
1479-7364
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1186/s40246-018-0171-5
info:eu-repo/semantics/altIdentifier/url/https://humgenomics.biomedcentral.com/articles/10.1186/s40246-018-0171-5
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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