Red blood cells function as reservoirs of tumor DNA

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Novel screening techniques for early lung cancer detection are crucial.
• Circulating tumor cell-free DNA (ctDNA) shows promise for biopsy-free tumor genotyping but faces sensitivity limitations due to scarcity and short half-life.
• Red blood cells (RBCs) sequester mitochondrial DNA, representing an unrecognized reservoir for circulating nucleic acids.

Purpose of the Study:

• To investigate RBCs as a potential reservoir for tumor DNA.
• To explore the utility of RBC-bound tumor DNA for early non-small cell lung cancer (NSCLC) detection.
• To establish a novel, biopsy-free approach for lung cancer diagnostics.

Main Methods:

• Co-culturing lung cancer cell lines (with KRAS and EGFR mutations) with RBCs.
• Detecting RBC-bound tumor DNA using quantitative polymerase chain reaction (qPCR).
• Comparing RBC-bound tumor DNA levels in early-stage NSCLC patients and healthy controls.

Main Results:

• RBCs acquired tumor DNA from lung cancer cell lines harboring KRAS and EGFR mutations.
• RBC-bound tumor DNA was detectable in patients with early-stage NSCLC.
• RBC-bound tumor DNA was not detected in healthy controls.

Conclusions:

• RBCs serve as a previously unrecognized reservoir for tumor DNA.
• RBC-bound tumor DNA detection offers a promising, biopsy-free method for early lung cancer diagnostics.
• This approach enhances the sensitivity and clinical utility of noninvasive cancer detection methods.