ASPH and hepatocellular carcinoma: Both of these features are hallmarks of mtDNA instability in HCC.12, 13, 19, 28 ASPH overexpression in HepG2 and Huh-7 cells significantly increased mutation frequency in the D-loop region and decreased copy numbers of D-loop and ND-1 region, the most frequently altered mtDNA region during tumorigenesis.