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

Autor: Pablo G. Mele, Florencia Cecilia Cardoso, Natalia C Liria, Ignacio Diaz Perez, Leonardo Sganga, Angela R. Solano, Ernesto J. Podestá, Susana Goncalves
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
BRCA1/2 and ovarian cancer
endocrine system diseases
Poly (ADP-Ribose) Polymerase-1
lcsh:Medicine
Medicina Clínica
medicine.disease_cause
Germline
Oncología
iPARP treatment
0302 clinical medicine
purl.org/becyt/ford/3.2 [https]
Drug Discovery
Aged
80 and over
Ovarian Neoplasms
Mutation
education.field_of_study
BRCA1 Protein
Incidence (epidemiology)
BRCA1/2 AND OVARIAN CANCER
Middle Aged
BRCA2 Protein
OVARIAN CANCER
IPARP TREATMENT
030220 oncology & carcinogenesis
Molecular Medicine
purl.org/becyt/ford/3 [https]
Female
Primary Research
Adult
medicine.medical_specialty
CIENCIAS MÉDICAS Y DE LA SALUD
lcsh:QH426-470
Adolescent
Population
Breast Neoplasms
Poly(ADP-ribose) Polymerase Inhibitors
Young Adult
03 medical and health sciences
Breast cancer
Germline mutation
Ovarian cancer
Internal medicine
Genetics
medicine
Humans
education
Molecular Biology
Germ-Line Mutation
Aged
business.industry
lcsh:R
medicine.disease
lcsh:Genetics
030104 developmental biology
business
Zdroj: Human Genomics
Human Genomics, Vol 12, Iss 1, Pp 1-8 (2018)
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
ISSN: 1479-7364
DOI: 10.1186/s40246-018-0171-5
Popis: 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
Databáze: OpenAIRE
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