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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

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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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Acknowledgements

We would like to express our gratitude to the laboratory technicians Ángeles Moreno Locubiche, Patricia Pascual Gilabert and Teresa Manzano Baiazitova and the nurse Pilar Moya Martínez. We would also like to thank all residents who have contributed to this report.

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Authors and Affiliations

  1. Genomics Laboratory, Deparment of Clinical Analysis, Virgen de la Arrixaca University Clinical Hospital, Ctra. Madrid-Cartagena, s/n El Palmar, 30120, Murcia, Spain

    Xavier Gabaldó Barrios,  Mª Desamparados Sarabia Meseguer, Ana Isabel Sánchez Bermúdez, Ángeles Aliaga Baño, Verónica Castillo Guardiola, Pedro Martínez Hernández, Isabel Tovar Zapata, José Antonio Noguera Velasco & Francisco Ruiz Espejo

  2. Genetic Counseling Unit, Department of Oncology, Virgen de la Arrixaca University Clinical Hospital, Murcia, Spain

    Miguel Marín Vera, Pilar Sánchez Henarejos, Mª Rosario García Hernández, Encarna Cuevas Tortosa & José Luis Alonso Romero

  3. Genetic Counseling Unit, Department of Oncology, Morales Meseguer University General Hospital, Murcia, Spain

    José Antonio Macías Cerrolaza, Marta Zafra Poves & Francisco Ayala de la Peña

  4. Department of Pathology, Virgen de la Arrixaca University Clinical Hospital, Murcia, Spain

    Enrique Martínez Barba

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  1. Xavier Gabaldó Barrios
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  2. Mª Desamparados Sarabia Meseguer
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  3. Miguel Marín Vera
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  4. Ana Isabel Sánchez Bermúdez
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  8. Mª Rosario García Hernández
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  10. Ángeles Aliaga Baño
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  11. Verónica Castillo Guardiola
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  16. José Luis Alonso Romero
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Correspondence to Mª Desamparados Sarabia Meseguer.

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Gabaldó Barrios, X., Sarabia Meseguer, .D., Marín Vera, M. et al. 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. Familial Cancer 16, 477–489 (2017). https://doi.org/10.1007/s10689-017-9985-x

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