Germline mutations of breast cancer susceptibility genes through expanded genetic analysis in unselected Colombian patients.

Autor: Sierra-Díaz DC; School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia., Morel A; School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia., Fonseca-Mendoza DJ; School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia., Bravo NC; School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia., Molano-Gonzalez N; Clinical Research Group, School of Medicine and Health Science, Universidad del Rosario, Bogotá, Colombia., Borras M; Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia., Munevar I; Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia., Lema M; Clínica de Oncología Astorga, Medellín, Colombia., Idrobo H; Centro Médico Julián Coronel, Cali, Colombia., Trujillo D; Centro Médico Julián Coronel, Cali, Colombia., Serrano N; Hospital Internacional de Colombia HIC, Piedecuesta, Colombia., Orduz AI; Hospital Internacional de Colombia HIC, Piedecuesta, Colombia., Lopera D; Oncólogos del Occidente S.A.S, Manizales, Colombia., González J; Oncólogos del Occidente S.A.S, Manizales, Colombia., Rojas G; Oncólogos del Occidente S.A.S, Manizales, Colombia.; Oncologos del Occidente SAS, Pereira, Colombia., Londono-De Los Ríos P; Oncólogos del Occidente S.A.S, Manizales, Colombia.; Oncologos del Occidente SAS, Pereira, Colombia., Manneh R; SOHEC, Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia., Cabrera R; School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia.; Laboratorio de Biología Molecular y Pruebas Diagnósticas de Alta Complejidad, Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia., Rubiano W; Hospital Universitario Mayor Méderi, Bogotá, Colombia., de la Peña J; Hospital Universitario Mayor Méderi, Bogotá, Colombia., Quintero MC; Integrative IPS, Bogotá, Colombia., Mantilla W; Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia.; Fundación CTIC-Fundación Cardioinfantil, Instituto de Cardiología, Bogotá, Colombia., Restrepo CM; School of Medicine and Health Sciences, Center for Research in Genetics and Genomics (CIGGUR), Institute of Translational Medicine (IMT), Universidad Del Rosario, Bogotá, Colombia. carlos.restrepo@urosario.edu.co.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2024 Jun 18; Vol. 18 (1), pp. 68. Date of Electronic Publication: 2024 Jun 18.
DOI: 10.1186/s40246-024-00623-7
Abstrakt: Background: In Colombia and worldwide, breast cancer (BC) is the most frequently diagnosed neoplasia and the leading cause of death from cancer among women. Studies predominantly involve hereditary and familial cases, demonstrating a gap in the literature regarding the identification of germline mutations in unselected patients from Latin-America. Identification of pathogenic/likely pathogenic (P/LP) variants is important for shaping national genetic analysis policies, genetic counseling, and early detection strategies. The present study included 400 women with unselected breast cancer (BC), in whom we analyzed ten genes, using Whole Exome Sequencing (WES), know to confer risk for BC, with the aim of determining the genomic profile of previously unreported P/LP variants in the affected population. Additionally, Multiplex Ligation-dependent Probe Amplification (MLPA) was performed to identify Large Genomic Rearrangements (LGRs) in the BRCA1/2 genes. To ascertain the functional impact of a recurrent intronic variant (ATM c.5496 + 2_5496 + 5delTAAG), a minigene assay was conducted.
Results: We ascertained the frequency of P/LP germline variants in BRCA2 (2.5%), ATM (1.25%), BRCA1 (0.75%), PALB2 (0.50%), CHEK2 (0.50%), BARD1 (0.25%), and RAD51D (0.25%) genes in the population of study. P/LP variants account for 6% of the total population analyzed. No LGRs were detected in our study. We identified 1.75% of recurrent variants in BRCA2 and ATM genes. One of them corresponds to the ATM c.5496 + 2_5496 + 5delTAAG. Functional validation of this variant demonstrated a splicing alteration probably modifying the Pincer domain and subsequent protein structure.
Conclusion: This study described for the first time the genomic profile of ten risk genes in Colombian women with unselected BC. Our findings underscore the significance of population-based research, advocating the consideration of molecular testing in all women with cancer.
(© 2024. The Author(s).)
Databáze: MEDLINE
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