Deciphering the Spectrum of Mitochondrial DNA Mutations in Hepatocellular Carcinoma Using High-Throughput Sequencing

Gene Expression
Chang YuXiaoni Kong

Abstract

Accumulation of mitochondrial DNA (mtDNA) mutations has been proposed to contribute to the initiation and progression of tumors. By using high-throughput sequencing strategies, we measured 33 specimens including 11 hepatocellular carcinoma (HCC) tissues, 11 corresponding adjacent tissues, and 11 normal liver tissues. We identified 194 single nucleotide variants (SNVs; including insert and deletion) in 33 liver tissues, and 13 somatic novel mutations were detected, including 7 mutations in the coding region. One of the seven somatic mutations (T7609C, 91.09%) is synonymous, which does not change amino acid coding; the other four somatic mutations (T6115C, 65.74%; G8387A, 12.23%; G13121A, 93.08%; and T14180C, 28.22%) could result in amino acid substitutions, potentially leading to mitochondrial dysfunction. Furthermore, two mutations in tRNA might influence amino acid transportation. Consistent with a previous study, we also found that mtDNA copy number was significantly reduced in HCC tissues. Therefore, we established a mitochondrial genome depletion cell line ρ0 and revealed that mtDNA loss reduced proliferation and migration in HCC cells but promoted their resistance to 5-fluorouracil. Our results suggested that somatic mtDNA...Continue Reading

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Citations

Oct 11, 2019·Genome Biology and Evolution·Qi LiuYiqiang Zhao
Oct 19, 2019·Metabolites·Mélissa Léveillé, Jennifer L Estall
May 1, 2021·International Journal of Molecular Sciences·Miriam LongoPaola Dongiovanni

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