Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors
Por:
Perez-Amado, Carlos Jhovani, Tovar, Hugo, Gomez-Romero, Laura, Beltran-Anaya, Fredy Omar, Bautista-Pina, Veronica, Dominguez-Reyes, Carlos, Villegas-Carlos, Felipe, Tenorio-Torres, Alberto, Alfaro-Ruiz, Luis Alberto, Hidalgo-Miranda, Alfredo, Jimenez-Morales, Silvia
Publicada:
1 ene 2020
Resumen:
Studies have suggested a potential role of somatic mitochondrial mutations in cancer development. To analyze the landscape of somatic mitochondrial mutation in breast cancer and to determine whether mitochondrial DNA (mtDNA) mutational burden is correlated with overall survival (OS), we sequenced whole mtDNA from 92 matched-paired primary breast tumors and peripheral blood. A total of 324 germline variants and 173 somatic mutations were found in the tumors. The most common germline allele was 663G (12S), showing lower heteroplasmy levels in peripheral blood lymphocytes than in their matched tumors, even reaching homoplasmic status in several cases. The heteroplasmy load was higher in tumors than in their paired normal tissues. Somatic mtDNA mutations were found in 73.9% of breast tumors; 59% of these mutations were located in the coding region (66.7% non-synonymous and 33.3% synonymous). Although the CO1 gene presented the highest number of mutations, tRNA genes (T,C, and W), rRNA 12S, and CO1 and ATP6 exhibited the highest mutation rates. No specific mtDNA mutational profile was associated with molecular subtypes of breast cancer, and we found no correlation between mtDNA mutational burden and OS. Future investigations will provide insight into the molecular mechanisms through which mtDNA mutations and heteroplasmy shifting contribute to breast cancer development. © Copyright © 2020 Pérez-Amado, Tovar, Gómez-Romero, Beltrán-Anaya, Bautista-Piña, Dominguez-Reyes, Villegas-Carlos, Tenorio-Torres, Alfaro-Ruíz, Hidalgo-Miranda and Jiménez-Morales.
Filiaciones:
Perez-Amado, Carlos Jhovani:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Programa de Doctorado, Posgrado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México, Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Univ Nacl Autonoma Mexico, Posgrad Ciencias Bioquim, Programa Doctorado, Mexico City, DF, Mexico
Tovar, Hugo:
Genómica Computacional, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Genom Computac, Mexico City, DF, Mexico
Gomez-Romero, Laura:
Genómica Computacional, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Genom Computac, Mexico City, DF, Mexico
Beltran-Anaya, Fredy Omar:
Laboratorio de Investigación en Epidemiología Clínica y Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, Mexico
Univ Autonoma Guerrero, Fac Ciencias Quim Biol, Lab Invest Epidemiol Clin & Mol, Chilpancingo, Mexico
Bautista-Pina, Veronica:
Instituto de Enfermedades de la Mama, FUCAM, Mexico City, Mexico
FUCAM, Inst Enfermedades Mama, Mexico City, DF, Mexico
Dominguez-Reyes, Carlos:
Instituto de Enfermedades de la Mama, FUCAM, Mexico City, Mexico
FUCAM, Inst Enfermedades Mama, Mexico City, DF, Mexico
Villegas-Carlos, Felipe:
Instituto de Enfermedades de la Mama, FUCAM, Mexico City, Mexico
FUCAM, Inst Enfermedades Mama, Mexico City, DF, Mexico
Tenorio-Torres, Alberto:
Instituto de Enfermedades de la Mama, FUCAM, Mexico City, Mexico
FUCAM, Inst Enfermedades Mama, Mexico City, DF, Mexico
Alfaro-Ruiz, Luis Alberto:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Hidalgo-Miranda, Alfredo:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
Jimenez-Morales, Silvia:
Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
Inst Nacl Med Genom, Lab Genom Canc, Mexico City, DF, Mexico
|