J Cancer 2017; 8(19):4011-4017. doi:10.7150/jca.21218

Research Paper

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

Weiyang Li1, 2*✉, Yanwei Qi3*, Xiaofang Cui1✉, Yuhui Sun3, Qing Huo3, Yan Yang1, Xinyuan Wen1, Meihua Tan3, Shiyi Du3, Huali Zhang1, 2, Meng Zhang1, 2, Chuanxin Liu1, 2, Qingsheng Kong1, 2

1. Jining Medical University, Jining, Shandong 272067, China;
2. Collaborative Innovation Center for Birth Defect Research and Transformation of Shandong Province, Jining Medical University, Jining, Shandong 272067, China;
3. BGI-Shenzhen, Shenzhen, 518083, China.
* These authors contributed equally to this work

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Li W, Qi Y, Cui X, Sun Y, Huo Q, Yang Y, Wen X, Tan M, Du S, Zhang H, Zhang M, Liu C, Kong Q. Heteroplasmy and Copy Number Variations of Mitochondria in 88 Hepatocellular Carcinoma Individuals. J Cancer 2017; 8(19):4011-4017. doi:10.7150/jca.21218. Available from http://www.jcancer.org/v08p4011.htm

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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: Heteroplasmy, Mitochondrial Genome, Copy Number, Hepatocellular carcinoma.