Mitochondrial DNA Mutation Analysis in Breast Cancer : Shifting From Germline Heteroplasmy Toward Homoplasmy in Tumors
Copyright © 2020 Pérez-Amado, Tovar, Gómez-Romero, Beltrán-Anaya, Bautista-Piña, Dominguez-Reyes, Villegas-Carlos, Tenorio-Torres, Alfaro-Ruíz, Hidalgo-Miranda and Jiménez-Morales..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Frontiers in oncology - 10(2020) vom: 28., Seite 572954 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pérez-Amado, Carlos Jhovani [VerfasserIn] |
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| Links: |
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| Themen: |
Breast cancer |
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| Anmerkungen: |
Date Revised 17.11.2020 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fonc.2020.572954 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 | ||
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| 700 | 1 | |a Jiménez-Morales, Silvia |e verfasserin |4 aut | |
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