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Familial Cancer
Published in: Familial Cancer 4/2017

01-10-2017 | Original Article

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

Authors: Xavier Gabaldó Barrios, Mª Desamparados Sarabia Meseguer, Miguel Marín Vera, Ana Isabel Sánchez Bermúdez, José Antonio Macías Cerrolaza, Pilar Sánchez Henarejos, Marta Zafra Poves, Mª Rosario García Hernández, Encarna Cuevas Tortosa, Ángeles Aliaga Baño, Verónica Castillo Guardiola, Pedro Martínez Hernández, Isabel Tovar Zapata, Enrique Martínez Barba, Francisco Ayala de la Peña, José Luis Alonso Romero, José Antonio Noguera Velasco, Francisco Ruiz Espejo

Published in: Familial Cancer | Issue 4/2017

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Abstract

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.
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Metadata
Title
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
Authors
Xavier Gabaldó Barrios
Mª Desamparados Sarabia Meseguer
Miguel Marín Vera
Ana Isabel Sánchez Bermúdez
José Antonio Macías Cerrolaza
Pilar Sánchez Henarejos
Marta Zafra Poves
Mª Rosario García Hernández
Encarna Cuevas Tortosa
Ángeles Aliaga Baño
Verónica Castillo Guardiola
Pedro Martínez Hernández
Isabel Tovar Zapata
Enrique Martínez Barba
Francisco Ayala de la Peña
José Luis Alonso Romero
José Antonio Noguera Velasco
Francisco Ruiz Espejo
Publication date
01-10-2017
Publisher
Springer Netherlands
Published in
Familial Cancer / Issue 4/2017
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI
https://doi.org/10.1007/s10689-017-9985-x

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