Research Article

Mitochondrial tRNA mutations may be infrequent in hepatocellular carcinoma patients

Published: June 24, 2016
Genet. Mol. Res. 15(2): gmr7665 DOI: 10.4238/gmr.15027665

Abstract

Mitochondrial DNA mutations have been shown to play important roles in the pathogenesis of hepatocellular carcinoma (HCC). In particular, genes encoding mitochondrial tRNA (mt-tRNA) are hotspots for pathogenic mutations associated with HCC. Recently, an increasing number of studies have reported the involvement of such mutations in this disease. As a result, several mt-tRNA mutations associated with HCC have been described. Some of these are neutral polymorphisms and may not cause mitochondrial dysfunction. Moreover, the molecular mechanisms by which these pathogenic mutations result in HCC remain unclear. To address this problem, we evaluated five mt-tRNA variants (tRNAVal T1659C, tRNAAla G5650A, tRNAArg T10463C, tRNAGlu A14679G, and tRNAPro C15975T) implicated in the clinical manifestation of HCC in humans. We performed evolutionary conservation analysis and used a bioinformatic tool to predict the secondary structure of the mt-tRNAs carrying these mutations. Using an established pathogenicity scoring system, we classified T10463C and A14679G as neutral polymorphisms, and determined that the T1659C, G5650A, and C15975T variants should be regarded as pathogenic mutations. To the best of our knowledge, this is the first report to establish the pathogenicity of HCC-associated mt-tRNA mutations.

Mitochondrial DNA mutations have been shown to play important roles in the pathogenesis of hepatocellular carcinoma (HCC). In particular, genes encoding mitochondrial tRNA (mt-tRNA) are hotspots for pathogenic mutations associated with HCC. Recently, an increasing number of studies have reported the involvement of such mutations in this disease. As a result, several mt-tRNA mutations associated with HCC have been described. Some of these are neutral polymorphisms and may not cause mitochondrial dysfunction. Moreover, the molecular mechanisms by which these pathogenic mutations result in HCC remain unclear. To address this problem, we evaluated five mt-tRNA variants (tRNAVal T1659C, tRNAAla G5650A, tRNAArg T10463C, tRNAGlu A14679G, and tRNAPro C15975T) implicated in the clinical manifestation of HCC in humans. We performed evolutionary conservation analysis and used a bioinformatic tool to predict the secondary structure of the mt-tRNAs carrying these mutations. Using an established pathogenicity scoring system, we classified T10463C and A14679G as neutral polymorphisms, and determined that the T1659C, G5650A, and C15975T variants should be regarded as pathogenic mutations. To the best of our knowledge, this is the first report to establish the pathogenicity of HCC-associated mt-tRNA mutations.

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