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A Molecular Characterization of the Allelic Expression of the <i>BRCA1</i> Founder Δ9–12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer
oleh: Julieta Dominguez-Ortiz, Rosa M. Álvarez-Gómez, Rogelio Montiel-Manríquez, Alberto Cedro-Tanda, Nicolás Alcaraz, Clementina Castro-Hernández, Luis Bautista-Hinojosa, Laura Contreras-Espinosa, Leda Torres-Maldonado, Verónica Fragoso-Ontiveros, Yuliana Sánchez-Contreras, Rodrigo González-Barrios, Marcela Angélica De la Fuente-Hernández, María de la Luz Mejía-Aguayo, Ulises Juárez-Figueroa, Alejandra Padua-Bracho, Rodrigo Sosa-León, Gabriela Obregon-Serrano, Silvia Vidal-Millán, Paulina María Núñez-Martínez, Abraham Pedroza-Torres, Sergio Nicasio-Arzeta, Alfredo Rodríguez, Fernando Luna, Fernanda Cisneros-Soberanis, Sara Frías, Cristian Arriaga-Canon, Luis A. Herrera-Montalvo
Format: | Article |
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Diterbitkan: | MDPI AG 2024-06-01 |
Deskripsi
Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the <i>BRCA1</i> gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in <i>BRCA1</i> has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of <i>BRCA1</i> (<i>BRCA1<sup>Δ9–12</sup></i>), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV <i>BRCA1<sup>Δ9–12</sup></i> by analyzing the differential expression of both alleles compared with the homozygous <i>BRCA1</i> control group using RT–qPCR, and we describe the isoforms produced by the <i>BRCA1</i> wild-type and <i>BRCA1<sup>Δ9–12</sup></i> alleles using nanopore long-sequencing. Using the Kruskal–Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous <i>BRCA1</i> control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV <i>BRCA1<sup>Δ9–12</sup></i> and identifying which of them has developed cancer.