Mitogenomic Alterations in Breast Cancer: Identification of Potential Biomarkers of Risk and Prognosis
Por:
Pérez-Amado C.J., Bazan-Cordoba A., Gómez-Romero L., Ramírez-Bello J., Bautista-Piña V., Tenorio-Torres A., Ruvalcaba-Limón E., Villegas-Carlos F., Mendiola-Soto D.K., Hidalgo-Miranda A., Jiménez-Morales S.
Publicada:
1 ene 2025
Resumen:
Alterations in the mitochondrial genome (mtDNA) have been shown to be key in cancer development and could be useful as biomarkers for diagnosis, prognosis, and treatment. To identify mtDNA variants associated with breast cancer, we analyzed the whole mtDNA sequence from paired tissues (tumor–peripheral blood) of women with this malignancy and from peripheral blood samples of healthy women. The mtDNA mutational landscape, heteroplasmy levels of the variants, and mitochondrial ancestry were established. Comparative analysis between cases and controls revealed significant differences in the number and location of variants, as well as in the heteroplasmy levels. Cases showed higher mutation number in MT-ND5, tRNAs, and rRNAs genes; increased proportion of missense variants; and elevated mtDNA content, than controls. Notably, a high blood mtDNA mutational burden (OR = 3.83, CI: 1.89–7.95, p = 5.3 × 10-5) and five mtDNA variants showed association with the risk of breast cancer. Furthermore, a low tumor mutational burden (HR = 7.82, CI: 1.0–63.6, p = 0.05) and the haplogroup L (HR = 12.16, CI: 2.0–72.8, p = 0.0062) were associated with decreased overall and disease-free survival, respectively. Our study adds evidence of the potential usefulness of mtDNA variants as risk and prognosis biomarkers for breast cancer. © 2025 by the authors.
Filiaciones:
Pérez-Amado C.J.:
Laboratorio de Innovación y Medicina de Precisión Núcleo “A”, Instituto Nacional de Medicina Genómica, Mexico City, 14610, Mexico
Bazan-Cordoba A.:
Laboratorio de Innovación y Medicina de Precisión Núcleo “A”, Instituto Nacional de Medicina Genómica, Mexico City, 14610, Mexico
Programa de Maestría y Doctorado, Posgrado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Gómez-Romero L.:
Subdirección de Bioinformática, Instituto Nacional de Medicina Genómica, Mexico City, 14610, Mexico
School of Medicine and Health Sciences, Tecnológico de Monterrey, Mexico City, 14380, Mexico
Ramírez-Bello J.:
Subdirección de Investigación Clínica, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, 14080, Mexico
Bautista-Piña V.:
Fundación de Cáncer de Mama, FUCAM, Mexico City, 04980, Mexico
Tenorio-Torres A.:
Fundación de Cáncer de Mama, FUCAM, Mexico City, 04980, Mexico
Ruvalcaba-Limón E.:
Fundación de Cáncer de Mama, FUCAM, Mexico City, 04980, Mexico
Villegas-Carlos F.:
Fundación de Cáncer de Mama, FUCAM, Mexico City, 04980, Mexico
Mendiola-Soto D.K.:
Laboratorio de Innovación y Medicina de Precisión Núcleo “A”, Instituto Nacional de Medicina Genómica, Mexico City, 14610, Mexico
Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, Mexico
Hidalgo-Miranda A.:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, 14610, Mexico
Jiménez-Morales S.:
Laboratorio de Innovación y Medicina de Precisión Núcleo “A”, Instituto Nacional de Medicina Genómica, Mexico City, 14610, Mexico
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