Mature Red Blood Cells Contain Long DNA Fragments and Could Acquire DNA from Lung Cancer Tissue

Abstract Red blood cells (RBC) are commonly known as cells with no nucleus or mitochondria and are assumed to be a transportation vehicle. This study confirms that RBC contain long DNA fragments inside with stain by both microscope and flow cytometry, which covers most nuclear and mitochondrial genome regions by next‐generation sequencing (NGS). Such characteristics demonstrate a significant difference compared with A549 cell line or paired peripheral blood mononuclear cell as nucleated cells. To further explore the characteristics of RNA DNA, DNA from 20 RBC samples is sequenced by NGS. Interestingly, several gaps and multiple regions with copy number variation are observed significantly different between different samples, which could be used to distinguish samples with different health status accurately. Using an in vitro co‐culture system, it is shown that RBC could absorb DNA‐bearing tumorigenic mutations from cancer cell lines but requires cell‐to‐cell contact. Finally, based on a small scale clinical trial, it is confirmed that common genetic mutations of cancer tissues could be detected in RBC from patients with early‐stage non‐small‐cell lung cancer. This study highlights a new biological phenomenon involving RBC and its translational potential as a novel liquid biopsy technology platform for early cancer screening and diagnosis of malignancy.