<abstract xmlns="http://www.w3.org/1999/xhtml">

Damage of mitochondrial functions caused by mitochondrial DNA (mtDNA) pathogenic mutations had long been proposed to be involved in breast carcinogenesis. However, the detailed pathological mechanism remained deeply undetermined. In this case-control study, we screened the frequencies of mitochondrial tRNA (mt-tRNA) mutations in 80 breast cancer tissues and matched normal adjacent tissues. PCR and Sanger sequence revealed five possible pathogenic mutations: <italic>tRNAVal</italic> G1606A, <italic>tRNAIle</italic> A4300G, <italic>tRNA</italic><italic>Ser</italic>(UCN) T7505C, <italic>tRNAGlu</italic> A14693G and <italic>tRNAThr</italic> G15927A. We noticed that these mutations resided at extremely conserved positions of tRNAs and would affect tRNAs transcription or modifications. Furthermore, functional analysis suggested that patients with these mt-tRNA mutations exhibited much lower levels of mtDNA copy number and ATP, as compared with controls (p&lt;0.05). Therefore, it can be speculated that these mutations may impair mitochondrial protein synthesis and oxidative phosphorylation (OXPHOS) complexes, which caused mitochondrial dysfunctions that were involved in the breast carcinogenesis. Taken together, our data indicated that mutations in mt-tRNA were the important contributors to breast cancer, and mutational analyses of mt-tRNA genes were critical for prevention of breast cancer.
</abstract>

Damage of mitochondrial functions caused by mitochondrial DNA (mtDNA) pathogenic mutations had long been proposed to be involved in breast carcinogenesis. However, the detailed pathological mechanism remained deeply undetermined. In this case-control study, we screened the frequencies of mitochondrial tRNA (mt-tRNA) mutations in 80 breast cancer tissues and matched normal adjacent tissues. PCR and Sanger sequence revealed five possible pathogenic mutations: tRNAVal G1606A, tRNAIle A4300G, tRNASer(UCN) T7505C, tRNAGlu A14693G and tRNAThr G15927A. We noticed that these mutations resided at extremely conserved positions of tRNAs and would affect tRNAs transcription or modifications. Furthermore, functional analysis suggested that patients with these mt-tRNA mutations exhibited much lower levels of mtDNA copy number and ATP, as compared with controls (p<0.05). Therefore, it can be speculated that these mutations may impair mitochondrial protein synthesis and oxidative phosphorylation (OXPHOS) complexes, which caused mitochondrial dysfunctions that were involved in the breast carcinogenesis. Taken together, our data indicated that mutations in mt-tRNA were the important contributors to breast cancer, and mutational analyses of mt-tRNA genes were critical for prevention of breast cancer.

Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

{"article-title":"Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer"}

Damage of mitochondrial functions caused by mitochondrial DNA (mtDNA) pathogenic mutations had long been proposed to be involved in breast carcinogenesis....

Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer

Article Category: ORIGINAL ARTICLE

Published Online: May 02, 2023

Page range: 15 - 22

DOI: https://doi.org/10.2478/bjmg-2022-0020

Keywords
breast cancer, mitochondrial tRNAs, mutations, carcinogenesis, pathogenic, mitochondrial dysfunction

© 2022 Ding H.J. et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Analysis of Mitochondrial Transfer RNA Mutations in Breast Cancer

Article Category: ORIGINAL ARTICLE

Published Online: May 02, 2023

Page range: 15 - 22

DOI: https://doi.org/10.2478/bjmg-2022-0020

Keywordsbreast cancer, mitochondrial tRNAs, mutations, carcinogenesis, pathogenic, mitochondrial dysfunction

© 2022 Ding H.J. et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
breast cancer, mitochondrial tRNAs, mutations, carcinogenesis, pathogenic, mitochondrial dysfunction