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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/86770
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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 Técnicas2025-09-29T10:24:28Zoai: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:34982025-09-29 10:24:28.493CONICET 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 |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.070432 |