Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors
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 wh...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.572954/full |
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| author | Carlos Jhovani Pérez-Amado Carlos Jhovani Pérez-Amado Hugo Tovar Laura Gómez-Romero Fredy Omar Beltrán-Anaya Verónica Bautista-Piña Carlos Dominguez-Reyes Felipe Villegas-Carlos Alberto Tenorio-Torres Luis Alberto Alfaro-Ruíz Alfredo Hidalgo-Miranda Silvia Jiménez-Morales |
| author_facet | Carlos Jhovani Pérez-Amado Carlos Jhovani Pérez-Amado Hugo Tovar Laura Gómez-Romero Fredy Omar Beltrán-Anaya Verónica Bautista-Piña Carlos Dominguez-Reyes Felipe Villegas-Carlos Alberto Tenorio-Torres Luis Alberto Alfaro-Ruíz Alfredo Hidalgo-Miranda Silvia Jiménez-Morales |
| author_sort | Carlos Jhovani Pérez-Amado |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T04:49:56Z |
| format | Article |
| id | doaj.art-2a4bfa5a02ae41309f0a3bcd859641ef |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T04:49:56Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-2a4bfa5a02ae41309f0a3bcd859641ef2022-12-22T03:47:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-10-011010.3389/fonc.2020.572954572954Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in TumorsCarlos Jhovani Pérez-Amado0Carlos Jhovani Pérez-Amado1Hugo Tovar2Laura Gómez-Romero3Fredy Omar Beltrán-Anaya4Verónica Bautista-Piña5Carlos Dominguez-Reyes6Felipe Villegas-Carlos7Alberto Tenorio-Torres8Luis Alberto Alfaro-Ruíz9Alfredo Hidalgo-Miranda10Silvia Jiménez-Morales11Laboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, MexicoPrograma de Doctorado, Posgrado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México, Mexico City, MexicoGenómica Computacional, Instituto Nacional de Medicina Genómica, Mexico City, MexicoGenómica Computacional, Instituto Nacional de Medicina Genómica, Mexico City, MexicoLaboratorio de Investigación en Epidemiología Clínica y Molecular, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero, Chilpancingo, MexicoInstituto de Enfermedades de la Mama, FUCAM, Mexico City, MexicoInstituto de Enfermedades de la Mama, FUCAM, Mexico City, MexicoInstituto de Enfermedades de la Mama, FUCAM, Mexico City, MexicoInstituto de Enfermedades de la Mama, FUCAM, Mexico City, MexicoLaboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, MexicoLaboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, MexicoLaboratorio de Genómica del Cáncer, Instituto Nacional de Medicina Genómica, Mexico City, MexicoStudies 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.https://www.frontiersin.org/articles/10.3389/fonc.2020.572954/fullmitochondrial DNAbreast cancermutationsheteroplasmyhaplogroupsmolecular subtypes |
| spellingShingle | Carlos Jhovani Pérez-Amado Carlos Jhovani Pérez-Amado Hugo Tovar Laura Gómez-Romero Fredy Omar Beltrán-Anaya Verónica Bautista-Piña Carlos Dominguez-Reyes Felipe Villegas-Carlos Alberto Tenorio-Torres Luis Alberto Alfaro-Ruíz Alfredo Hidalgo-Miranda Silvia Jiménez-Morales Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors Frontiers in Oncology mitochondrial DNA breast cancer mutations heteroplasmy haplogroups molecular subtypes |
| title | Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors |
| title_full | Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors |
| title_fullStr | Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors |
| title_full_unstemmed | Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors |
| title_short | Mitochondrial DNA Mutation Analysis in Breast Cancer: Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors |
| title_sort | mitochondrial dna mutation analysis in breast cancer shifting from germline heteroplasmy toward homoplasmy in tumors |
| topic | mitochondrial DNA breast cancer mutations heteroplasmy haplogroups molecular subtypes |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.572954/full |
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