Red Blood Cells Function as Reservoirs of Tumor DNA
Novel screening techniques for early detection of lung cancer are urgently needed. Profiling circulating tumor cell-free DNA (ctDNA) has emerged as a promising tool for biopsy-free tumor genotyping. However, both the scarcity and short half-life of ctDNA substantially limit the sensitivity and clinical utility of ctDNA detection methodologies. Our discovery that Red Blood Cells (RBCs) sequester mitochondrial DNA opens a new avenue for detecting circulating nucleic acids, as RBCs represent an unrecognized reservoir of circulating nucleic acid. Here, we show that RBCs acquire tumor DNA following co-culture with lung cancer cell lines harboring KRAS and EGFR mutations. RBC-bound tumor DNA is detectable in patients with early-stage Non-Small Cell Lung Cancer (NSCLC) but not in healthy controls by qPCR. Our results collectively uncover a previously unrecognized yet easily accessible reservoir of tumor DNA, offering a promising foundation for future RBC-based tumor diagnostics.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
American journal of physiology. Lung cellular and molecular physiology - (2024) vom: 26. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Thompson, Jeffrey C [VerfasserIn] |
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| Anmerkungen: |
Date Revised 26.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1152/ajplung.00049.2024 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370191137 |
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| 520 | |a Novel screening techniques for early detection of lung cancer are urgently needed. Profiling circulating tumor cell-free DNA (ctDNA) has emerged as a promising tool for biopsy-free tumor genotyping. However, both the scarcity and short half-life of ctDNA substantially limit the sensitivity and clinical utility of ctDNA detection methodologies. Our discovery that Red Blood Cells (RBCs) sequester mitochondrial DNA opens a new avenue for detecting circulating nucleic acids, as RBCs represent an unrecognized reservoir of circulating nucleic acid. Here, we show that RBCs acquire tumor DNA following co-culture with lung cancer cell lines harboring KRAS and EGFR mutations. RBC-bound tumor DNA is detectable in patients with early-stage Non-Small Cell Lung Cancer (NSCLC) but not in healthy controls by qPCR. Our results collectively uncover a previously unrecognized yet easily accessible reservoir of tumor DNA, offering a promising foundation for future RBC-based tumor diagnostics | ||
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| 700 | 1 | |a Jose, Joshua S |e verfasserin |4 aut | |
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| 700 | 1 | |a Gupta, Aasha |e verfasserin |4 aut | |
| 700 | 1 | |a Eruslanov, Evgeniy |e verfasserin |4 aut | |
| 700 | 1 | |a Singhal, Sunil |e verfasserin |4 aut | |
| 700 | 1 | |a Albelda, Steven M |e verfasserin |4 aut | |
| 700 | 1 | |a Mangalmurti, Nilam S |e verfasserin |4 aut | |
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