A Molecular Characterization of the Allelic Expression of the BRCA1 Founder Δ9–12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer

Author:

Dominguez-Ortiz Julieta123,Álvarez-Gómez Rosa M.3,Montiel-Manríquez Rogelio1ORCID,Cedro-Tanda Alberto4ORCID,Alcaraz Nicolás5,Castro-Hernández Clementina1ORCID,Bautista-Hinojosa Luis1,Contreras-Espinosa Laura1ORCID,Torres-Maldonado Leda6ORCID,Fragoso-Ontiveros Verónica3,Sánchez-Contreras Yuliana3,González-Barrios Rodrigo1ORCID,Fuente-Hernández Marcela Angélica De la3,Mejía-Aguayo María de la Luz3,Juárez-Figueroa Ulises6ORCID,Padua-Bracho Alejandra3,Sosa-León Rodrigo3,Obregon-Serrano Gabriela3,Vidal-Millán Silvia3ORCID,Núñez-Martínez Paulina María3,Pedroza-Torres Abraham3ORCID,Nicasio-Arzeta Sergio7ORCID,Rodríguez Alfredo68,Luna Fernando1ORCID,Cisneros-Soberanis Fernanda9ORCID,Frías Sara68ORCID,Arriaga-Canon Cristian110,Herrera-Montalvo Luis A.110ORCID

Affiliation:

1. Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Avenida San Fernando No. 22 Col. Sección XVI, Tlalpan, Mexico City 14080, Mexico

2. Instituto Nacional de Cancerología, Universidad Nacional Autónoma de México (UNAM), Coyoacán, Mexico City 04510, Mexico

3. Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Av. San Fernando No. 22 Col. Sección XVI, Tlalpan, Mexico City 14080, Mexico

4. Núcleo B de Innovación en Medicina de Precisión, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal Tepepan, Tlalpan, Mexico City 14610, Mexico

5. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3A, 2200 Copenhagen, Denmark

6. Instituto Nacional de Pediatría, Insurgentes Sur No. 3700-C. Coyoacán, Mexico City 04530, Mexico

7. Natural Resource Ecology Laboratory, Colorado State University, Fort Collins, CO 80521, USA

8. Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), México City 04510, Mexico

9. Wellcome Trust Centre for Cell Biology, ICB, University of Edinburgh, Michael Swann Building, King’s Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK

10. Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64710, Mexico

Abstract

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 BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 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 BRCA1 (BRCA1Δ9–12), 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 BRCA1Δ9–12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT–qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9–12 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 BRCA1 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 BRCA1Δ9–12 and identifying which of them has developed cancer.

Funder

“Programa presupuestario Anexo 13 del Decreto de PEF: 309 Clínica de Cáncer Hereditario”

Consejo Nacional de Humanidades, Ciencias y Tecnologías (CONAHCYT), Mexico

Publisher

MDPI AG

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3