Heteroplasmy and Copy Number Variations of Mitochondria in 88 Hepatocellular Carcinoma Individuals

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. In this study, we had analysed the copy number variations and heteroplasmic mutations of mitochondria (MT) in 88 HCC individuals. The average copy number of MT genome in normal samples was significantly greater than that in tumor samples. Overall, the number of heteroplasmic mutations in 88 tumor and their matched normal samples were 241 and 173, respectively. There was higher positive ratio of heteroplasmic mutations in tumor samples (86%) than normal samples (73%). Worthwhile mention, ND1 gene harbored greater mutation frequency and more nonsynonymous mutations in tumor samples. Interestingly, 202 tumor-specific heteroplasmic mutations were detected. Moreover, ND1, ND3, ND4, ND5 and ND6 genes had higher ratio of nonsynonymous versus synonymous mutations in tumor-specific heteroplasmic mutations. It might suggest that the disorder of NADH dehydrogenase (complex I) resulted by heteroplasmic mutations may have close relation with tumorigenesis of hepatocellular carcinoma. This study provided theoretical basis for further understanding mechanism of tumorigenesis from the perspective of mitochondrial heteroplasmic mutations.

Keywords: Copy Number; Hepatocellular carcinoma.; Heteroplasmy; Mitochondrial Genome.

Figure 1

The copy number and heteroplasmic mutations of tumor and normal samples (a) represented that the difference of copy number variation in tumor and normal samples (T-test, p<0.01). (b) represented the difference of the ratio of samples with heteroplasmic mutations between tumor and normal samples (Chi-squared test, p<0.01). (c)represented that comparing the heteroplasmic ratio of heteroplasmic mutations in tumor and normal samples (T-test, p<0.05) and comparing the heteroplasmic ratio of nonsynonymous mutations in tumor and normal samples (T-test, p<0.05).

Figure 2

The distribution of mutation frequency of heteroplasmic sites in tumor and normal samples. The figure showed the distribution of mutation frequency in tumor and normal samples. The inner circle revealed the distribution of mutation frequency in normal samples and the outer circle revealed the distribution of mutation frequency in tumor samples.

Figure 3

Comparison of mutation frequency between tumor and normal samples The figure showed the difference of mutation frequency in tumor and normal samples. The inner circle revealed the distribution of gene frequency in normal samples and the outer circle revealed the distribution of gene frequency in tumor samples.