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The size of cell-free mitochondrial DNA in blood is inversely correlated with tumor burden in cancer patients.

  • Author(s): An, Qin
  • Hu, Youjin
  • Li, Qingjiao
  • Chen, Xufeng
  • Huang, Jiaoti
  • Pellegrini, Matteo
  • Zhou, Xianghong Jasmine
  • Rettig, Matthew
  • Fan, Guoping
  • et al.
Abstract

Circulating cell-free DNAs (cfDNAs) are fragmented DNA molecules released into the blood by cells. Previous studies have suggested that mitochondria-originated cfDNA fragments (mt-cfDNAs) in cancer patients are more fragmented than those from healthy controls. However, it is still unknown where these short mt-cfDNAs originate, and whether the length of mt-cfDNAs can be correlated with tumor burden and cancer progression. In this study, we first performed whole-genome sequencing analysis (WGS) of cfDNAs from a human tumor cell line-xenotransplantation mouse model and found that mt-cfDNAs released from transplanted tumor cells were shorter than the mouse counterpart. We next analyzed blood cfDNA samples from hepatocellular carcinoma and prostate cancer patients and found that mt-cfDNA lengths were inversely related to tumor size as well as the concentration of circulating tumor DNA. Our study suggested that monitoring the size of mt-cfDNAs in cancer patients would be a useful way to estimate tumor burden and cancer progression.

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