Dear Editor Extrachromosomal DNA (ecDNA), a major focal oncogene amplification mode found across cancer, has recently regained attention as an emerging cancer hallmark , with a pervasive presence across cancers . With technical advancements such as high-coverage sequencing and live-cell genome imaging, we can now investigate ecDNA's behaviors and functions . However, we still lack an understanding of how to eliminate ecDNA. We observed depletion of cells containing ecDNA during lentiviral but not transposon-based transduction while we sought to investigate the mechanism of ecDNA behavior. This discovery may provide critical information on utilizing a lentiviral system in emerging ecDNA research. Additionally, this observation suggests specific sensitivities for cells with ecDNA.
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http://dx.doi.org/10.1101/2025.02.22.639631 | DOI Listing |
Cancer Discov
March 2025
University of Copenhagen, Copenhagen, Denmark.
Extrachromosomal DNA (ecDNA) presents a promising target for cancer therapy; however, its spatial-temporal diversity and influence on tumor evolution and the immune microenvironment remain largely unclear. We apply computational methods to analyze ecDNA from whole-genome sequencing data of 595 urothelial carcinoma (UC) patients. We demonstrate that ecDNA drives clonal evolution through structural rearrangements during malignant transformation and recurrence of UC.
View Article and Find Full Text PDFDear Editor Extrachromosomal DNA (ecDNA), a major focal oncogene amplification mode found across cancer, has recently regained attention as an emerging cancer hallmark , with a pervasive presence across cancers . With technical advancements such as high-coverage sequencing and live-cell genome imaging, we can now investigate ecDNA's behaviors and functions . However, we still lack an understanding of how to eliminate ecDNA.
View Article and Find Full Text PDFPhilos Trans R Soc Lond B Biol Sci
March 2025
University of Otago, Dunedin 9054, New Zealand.
The ribosome consists of protein and RNA components. Deletion of genes encoding specific ribosomal proteins has revealed that heterogeneity in the ribosome must exist in vertebrates; however, this has not been tested for ribosomal RNA (rRNA). In zebrafish (), the '45S-M' ribosomal RNA-encoding locus undergoes massive extrachromosomal amplification during oocyte growth and ovary differentiation and is distinct from the regular ribosomal DNA (rDNA) locus encoding somatic rRNA (45S-S).
View Article and Find Full Text PDFNucleic Acids Res
February 2025
Department of Biology, University of Copenhagen, Copenhagen, DK-2200 Copenhagen N, Denmark.
Recent research reveals that eukaryotic genomes form circular DNA from all parts of their genome, some large enough to carry whole genes. In organisms like yeast and in human cancers, it is often observed that extrachromosomal circular DNA (eccDNA) benefits the individual cell by providing resources for rapid cellular growth. However, our comprehension of eccDNA remains incomplete, primarily due to their transient nature.
View Article and Find Full Text PDFHeliyon
February 2025
Department of Cancer and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Here, we analyze the viral landscape in blood and tissue from 4918 metastatic cancer patients across 38 solid cancer types from the Hartwig Medical Foundation (HMF) cohort, the largest pan-cancer study on metastatic cancer. Using a coverage-based filtering approach, we detected 25 unique viral genera across 32 different cancer types, with a total of 747 unique virus-positive tissue samples. We detected 336 virus-positive blood samples across 29 cancer types, dominated by and .
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