Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse.
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 pattern...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0327483 |
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| author | Ruiqing Fu He Amy Su Yi Zhao Yafei Tian Hongyan Chen Daru Lu |
| author_facet | Ruiqing Fu He Amy Su Yi Zhao Yafei Tian Hongyan Chen Daru Lu |
| author_sort | Ruiqing Fu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1925bd445dd74d3ab5fc7c927e953245 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-1925bd445dd74d3ab5fc7c927e9532452025-08-20T03:28:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01207e032748310.1371/journal.pone.0327483Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse.Ruiqing FuHe Amy SuYi ZhaoYafei TianHongyan ChenDaru LuCell-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.https://doi.org/10.1371/journal.pone.0327483 |
| spellingShingle | Ruiqing Fu He Amy Su Yi Zhao Yafei Tian Hongyan Chen Daru Lu Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse. PLoS ONE |
| title | Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse. |
| title_full | Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse. |
| title_fullStr | Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse. |
| title_full_unstemmed | Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse. |
| title_short | Dissecting cell-free DNA fragmentation variation in tumors using cell line-derived xenograft mouse. |
| title_sort | dissecting cell free dna fragmentation variation in tumors using cell line derived xenograft mouse |
| url | https://doi.org/10.1371/journal.pone.0327483 |
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