Molecular characterization and clinical interpretation of BRCA1/BRCA2 variants in families from Murcia (south-eastern Spain) with hereditary breast and ovarian cancer: clinical-pathological features in BRCA carriers and non-carriers
Autor: | Ana Isabel Sánchez Bermúdez, Xavier Gabaldó Barrios, Mª Rosario García Hernández, Enrique Martínez Barba, Francisco Ruiz Espejo, Mª de los Desamparados Sarabia Meseguer, José Antonio Noguera Velasco, Francisco Ayala de la Peña, Miguel Marín Vera, José Antonio Macías Cerrolaza, José Luis Alonso Romero, Ángeles Aliaga Baño, Marta Zafra Poves, Isabel Tovar Zapata, Pilar Sánchez Henarejos, Pedro Luis Martínez Hernández, Verónica Castillo Guardiola, Encarna Cuevas Tortosa |
---|---|
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty Heterozygote endocrine system diseases Genetic counseling Population Breast Neoplasms medicine.disease_cause 03 medical and health sciences Exon 0302 clinical medicine Breast cancer Internal medicine Genetics medicine Humans Genetic Predisposition to Disease Age of Onset skin and connective tissue diseases education Genetics (clinical) Triple-negative breast cancer Gynecology BRCA2 Protein Ovarian Neoplasms education.field_of_study Mutation business.industry BRCA1 Protein Genetic Variation Exons medicine.disease Human genetics Pedigree 030104 developmental biology Spain 030220 oncology & carcinogenesis Hereditary Breast and Ovarian Cancer Syndrome Female Ovarian cancer business |
Zdroj: | Familial cancer. 16(4) |
ISSN: | 1573-7292 |
Popis: | This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C > T) and the most frequently detected mutations were c.68_69delAG, c.212 + 1G > A, c.5123C > A, c.211A > G and c.1918C > T, which together represented 56.67% of total pathogenic mutations. In BRCA2 gene, four recurrent variants were described (deletion of entire exon 2, c.9117G > A, c.3264dupT and c.3455T > G) representing 43.5% of the mutations in this gene. Mutation c.68_69delAG and deletion of entire exon 2 in BRCA1 and BRCA2 genes respectively were the most prevalent variants in our population. Regarding the genotype-phenotype relation, mutation c.212 + 1G > A appeared in an important percentage of breast and ovarian cancer cases, c.5123C > A in bilateral breast cancer and c.9117G > A in bilateral breast cancer and ovarian cancer. With respect to clinical–pathological characteristic, BRCA1/BRCA2 mutation carriers showed earlier onset age of breast tumour and higher risk of developing contra lateral breast cancer than non-informative cases. Moreover, association between either molecular subtype triple negative breast cancer or ovarian cancer and BRCA1 carriers was obtained. |
Databáze: | OpenAIRE |
Externí odkaz: |