However, high levels of ccf-DNA observed in patients with cancer may not come from either neoplastic cells or from surrounding normal epithelial cells from the tumor’s tissue-of-origin (Mattox et al, 2023), suggesting that cancer may have a systemic effect on protein-binding of the mitochondrial genome or plasma environments to influence ccf-mtDNA fragmentomics. The gene discussed is PITX1; the disease is cancer.