Browsing by Subject "Novel mutations"

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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
    (Springer, 2017-05-05) Gabaldó Barrios, Xavier; Marín Vera, Miguel; Sánchez Bermúdez, Ana Isabel; Macías Cerrolaza, José Antonio; Sánchez Henarejos, Pilar; Zafra Poves, Marta; García Hernández, María Rosario; Cuevas Tortosa, Encarna; Aliaga Baño, Ángeles; Castillo Guardiola, Verónica; Martínez Hernández, Pedro; Tovar Zapata, Isabel; Martínez Barba, Enrique; Ayala de la Peña, Francisco; Alonso-Romero, José Luis; Noguera Velasco, José Antonio; Ruiz Espejo, Francisco; Sarabia Meseguer, María Desamparados; Medicina
    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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    New insights into the performance of multigene panel testing: two novel nonsense variants in BRIP1 and TP53 in a young woman with breast cancer
    (Elsevier, 2018-06-23) Castillo-Guardiola, Verónica; Marín-Vera, Miguel; Sánchez-Bermúdez, Ana Isabel; Alonso-Romero, José Luis; Noguera Velasco, José Antonio; Ruiz Espejo, Francisco; Sarabia Meseguer, María Desamparados; Medicina
    Li-Fraumeni syndrome is an autosomal-dominant disorder caused by germline mutations in the tumour suppressor gene TP53. Here we report the case of a family whose index case was a woman diagnosed with bilateral breast cancer at the age of 18 and who had a non-informative result after BRCA1 and BRCA2 testing. After extending the study through multigene panel testing, two clinically relevant variants in the TP53 and BRIP1 genes, respectively, were found. Afterwards, the patient developed a glioblastoma. Both tumours were consistent with Li-Fraumeni syndrome. Thanks to the possibility of studying different genes related with hereditary breast and ovarian cancer, it was possible to find out the gene variant that caused the early onset cancers in the patient. Furthermore, genetic counselling was provided to the index case and her family.