Sarabia Meseguer, María Desamparados

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Sarabia Meseguer, María Desamparados

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Sarabia Meseguer, María Desamparados

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Bioquímica y Biología Molecular "B" e Inmunología

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Novel BRCA1 deleterious mutation (c.1918C>T) in familial breast and ovarian cancer syndrome who share a common ancestry
(Springer, 2014-03-16) Gabaldó Barrios, Xavier; Alonso-Romero, José Luis; Marín Vera, Miguel; Marín Zafra, Gema; Sánchez Henarejos, Pilar; Sánchez Bermúdez, Ana Isabel; Ruiz Espejo, Francisco; Sarabia Meseguer, María Desamparados; Medicina
Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA repair processes resulting in elevated genome instability and predisposing to breast and ovarian cancer. We report a novel mutation (c.1918C>T) in the exon 11 of the BRCA1 gene that consists of a nonsense mutation that causes a stop codon downstream in the 640 position of the protein. The mutation was present in two Spanish unrelated families and was associated with four breast cancer cases, including two bilateral breast cancer (one of them synchronous). The median age/mean age (range) was 48.5/44.25 years (27–53). This finding led us to perform haplotype analysis in all family carriers. Four highly polymorphic microsatellite markers were used (17-3858, 17-3930, D17S855, D17S1326) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common haplotype. None of the noncarriers of the mutation or of the 24 healthy controls showed this haplotype. Therefore, the c.1918C>T mutation carriers from these two families allows us to assert that all analyzed mutation carriers share a common ancestry.
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Obtención y purificación de enzimas implicadas en la determinación de colesterol : colesterol oxidasa y nadh peroxidasa / Amparo Sarabia Meseguer ; dirigida por Francisco García Carmona y Alvaro Sánchez Ferrer.
(Murcia : Universidad de Murcia, Facultad de Biología,, 2002) Sarabia Meseguer, María Desamparados
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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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Recurrent genetic variants and prioritization of variants of uncertain clinical significance associated with hereditary breast and ovarian cancer in families from the Region of Murcia
(De Gruyter, 2023-09-22) Rosado-Jiménez, Laura; Mestre-Terkemani, Younes; García-Aliaga, Ángeles; Marín-Vera, Miguel; Macías-Cerrolaza, José Antonio; García-Hernández, María Rosario; Zafra-Poves, Marta; Sánchez-Henarejos, Pilar; Ayala de la Peña, Francisco; Alonso-Romero, José Luis; Noguera Velasco, José Antonio; Ruiz Espejo, Francisco; Sarabia Meseguer, María Desamparados; Medicina
Objectives Hereditary breast and ovarian cancer (HBOC) follows an autosomal dominant inheritance pattern of cancer susceptibility genes. The risk of developing this disease is primarily associated with germline mutations in the BRCA1 and BRCA2 genes. The advent of massive genetic sequencing technologies has expanded the mutational spectrum of this hereditary syndrome, thereby increasing the number of variants of uncertain clinical significance (VUS) detected by genetic testing. Methods A prevalence study of HBOC was performed within 2,928 families from the Region of Murcia, in southeastern Spain. Genetic testing enabled the identification of recurrent pathogenic variants and founder mutations, which were mainly related to the BRCA1 and BRCA2 genes. VUS testing was performed using a prioritization algorithm designed by our working group. Results Variants c.68_69del, c.212+1G>A, and c.5123C>A were detected in 30 % of BRCA1 carriers, whereas exon 2 deletion concurrent with c.3264dupT, c.3455T>G and c.9117G>A variants were found in 30 % of BRCA2 carriers. A total of 16 VUS (15 %) were prioritized. Conclusions The genotype-phenotype correlation observed in our study is consistent with the scientific literature. Furthermore, the founder effect of c.1918C>T (BRCA1) and c.8251_8254del (ATM) was verified in the Murcian population, whereas exon 2 deletion (BRCA2) was proven to be a Spanish founder mutation. Our algorithm enabled us to prioritize potentially pathogenic VUS that required further testing to determine their clinical significance and potential role in HBOC.
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Mutational analysis of RAD51C and RAD51D genes in hereditary breast and ovarian cancer families from Murcia (southeastern Spain)
(Elsevier, 2018-02-02) Sánchez-Bermúdez, Ana Isabel; García-Aliaga, Ángeles; Marín-Vera, Miguel; Macías-Cerrolaza, José Antonio; Sánchez Henaréjos, Pilar; Guardiola-Castillo, Verónica; Ayala-de la Peña, Francisco; Alonso-Romero, José Luis; Noguera Velasco, José Antonio; Ruiz Espejo, Francisco; Sarabia Meseguer, María Desamparados; Medicina
RAD51C and RAD51D have been defined as susceptibility genes for hereditary breast and ovarian cancer syndrome in several studies. In the present study, a mutation analysis of these genes was performed on non BRCA1/2 families. RAD51C and RAD51D genes were analyzed in 141 and 77 families, respectively. The analysis included direct sequencing and multiple ligation probe analysis. The RAD51C pathogenic variant c.404G > A was identified in a breast and ovarian cancer family (0.7%), while the RAD51D pathogenic variant c.694C > T was described in an ovarian cancer family (1.3%). Moreover, three unknown clinical significance variants were detected: c.307T > G in RAD51C, and c.413A > G and c.715C > T in RAD51D. No large genomic rearrangements (LGRs) were found. RAD51D carriers suffered from premenopausal ovarian tumors. These results increase our knowledge about the RAD51C and RAD51D mutation spectrum and support the notion that these genes should be included in the gene panel testing performed on patients with hereditary breast and ovarian cancer syndrome.
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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.
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Next step in molecular genetics of hereditary breast/ovarian cancer: Multigene panel testing in clinical actionably genes and prioritization algorithms in the study of variants of uncertain significance
(Elsevier, 2022-03-01) Castillo-Guardiola, Verónica; Rosado-Jiménez, Laura; Marín-Vera, Miguel; Macías-Cerrolaza, José Antonio; García-Hernández, Rosario; Zafra-Poves, Marta; Sánchez-Henarejos, Pilar; Moreno-Locubiche, María Ángeles; Cuevas-Tortosa, Encarnación; Arnaldos-Carrillo, María; Ayala de la Peña, Francisco; Alonso-Romero, José Luis; Noguera Velasco, José Antonio; Ruiz Espejo, Francisco; Sarabia Meseguer, María Desamparados; Medicina
Introduction: BRCA1 and BRCA2 are the two main genes causing hereditary breast and ovarian cancer (HBOC). However, thanks to the development of Next Generation Sequencing (NGS), other genes linked to this syndrome (CHEK2, BRIP1, ATM and PALB2 among others) can be analysed. Material and methods: an analysis by multigene panel testing was performed in 138 index cases (ICs) from HBOC Spanish families with a previous non-informative result for BRCA1/2. The BRCA Hereditary Cancer Master™ Plus kit, including 26 actionable and candidate genes related to HBOC was employed. Once classified, an algorithm was employed to prioritized those variants of unknown significance with a higher risk of having a deleterious effect. Moreover, a mRNA splicing assay was performed for the prioritized VUS c.3402+3A > C in ATM, located at intron 23. Results: A total of 82 variants were found: 70 VUS and 12 pathogenic or probably pathogenic variants. The diagnostic yield in actionable genes non-BRCA was 7.97% of the total tested ICs. Overall, 19 VUS were prioritized, which meant 27% of the 70 total VUS. RNA analysis of the variant 3402+3A > C confirmed a deleterious impact on splicing. Discussion: The implementation of a multigene panel in HBOC studied families improved the diagnostic yield, concordant with results obtained in previous publications. Due to the important number of VUS obtained in NGS, the application of a prioritization algorithm is needed in order to select those variants in which it is necessary to conduct further studies.