Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse

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Publicado en:PLoS One vol. 20, no. 7 (Jul 2025), p. e0327483
Autor principal: Fu, Ruiqing
Otros Autores: He, Amy Su, Zhao, Yi, Tian, Yafei, Chen, Hongyan, Lu, Daru
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Public Library of Science
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024 7 |a 10.1371/journal.pone.0327483  |2 doi 
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100 1 |a Fu, Ruiqing 
245 1 |a Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse 
260 |b Public Library of Science  |c Jul 2025 
513 |a Journal Article 
520 3 |a Cell-free DNA (cfDNA) is increasingly studied for its diverse applications in non-invasive detection. Non-randomly cleaved by nucleases and released into the bloodstream, cfDNA exhibits a variety of intrinsic fragmentation patterns indicative of cell status. Particularly, these fragmentation patterns have recently been demonstrated to be effective in predicting cancer and its tissue-of-origin, owing to increased variation of fragmentation features observed in tumor patients. However, there remains a lack of detailed exploration of altered cfDNA fragmentation profiles in tumors, which consist of a mixture of both non-tumor cfDNA and circulating tumor DNA (ctDNA). Hence, we leveraged the human tumor cell line-derived xenograft (CDX) mouse model, where different tumor cell lines were implanted into different anatomical sites, to isolate pure ctDNA and separately investigate the fragment properties of CDX-cfDNA and ctDNA. We found an enrichment of short cfDNA fragments in both CDX-cfDNA and ctDNA compared to normal plasma cfDNA, with more elevated short fragments in ctDNA. Moreover, the CDX-cfDNA fragmentation features distinguished between CDX models of different tumor cell lines, while the ctDNA fragmentation features conversely discriminate between CDX models of different anatomical sites. The results suggested that both non-tumor cfDNA and ctDNA contribute to the increased variation observed in tumors, and that cfDNA fragmentation may be highly variable and susceptible to regulations by both original cells and cells within the local niche. 
653 |a Cancer 
653 |a DNA methylation 
653 |a Tumors 
653 |a Plasma 
653 |a Tumorigenesis 
653 |a Fragments 
653 |a Mutation 
653 |a Cell culture 
653 |a Variation 
653 |a Deoxyribonucleic acid--DNA 
653 |a Xenotransplantation 
653 |a Tumor cell lines 
653 |a Genomes 
653 |a Animal models 
653 |a DNA fragmentation 
653 |a Fragmentation 
653 |a Xenografts 
653 |a Environmental 
700 1 |a He, Amy Su 
700 1 |a Zhao, Yi 
700 1 |a Tian, Yafei 
700 1 |a Chen, Hongyan 
700 1 |a Lu, Daru 
773 0 |t PLoS One  |g vol. 20, no. 7 (Jul 2025), p. e0327483 
786 0 |d ProQuest  |t Health & Medical Collection 
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