Dataset Information

Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.

ABSTRACT: The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred. Cell targeting and ctDNA integration require ERVL, SINE or LINE DNA sequences. Chemically manufactured AluSp and MER11C sequences replicated multiple myeloma (MM) ctDNA cell targeting and integration. Additionally, we found that ctDNA may alter the treatment response of MM and pancreatic cancer models. This study shows that retrotransposon DNA sequences promote cancer gene transfer. However, because cell-free DNA has been detected in physiological and other pathological conditions, our findings have a broader impact than just cancer. Furthermore, the discovery that transposon DNA sequences mediate tissue-specific targeting will open up a new avenue for the delivery of genes and therapies.

SUBMITTER: Cinar M

PROVIDER: S-EPMC11260451 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.

Cinar Munevver M Martinez-Medina Lourdes L Puvvula Pavan K PK Arakelyan Arsen A Vardarajan Badri N BN Anthony Neil N Nagaraju Ganji P GP Park Dongkyoo D Feng Lei L Sheff Faith F Mosunjac Marina M Saxe Debra D Flygare Steven S Alese Olatunji B OB Kaufman Jonathan L JL Lonial Sagar S Sarmiento Juan M JM Lossos Izidore S IS Vertino Paula M PM Lopez Jose A JA El-Rayes Bassel B Bernal-Mizrachi Leon L

Nucleic acids research 20240701 13

The exchange of genes between cells is known to play an important physiological and pathological role in many organisms. We show that circulating tumor DNA (ctDNA) facilitates cell-specific gene transfer between human cancer cells and explain part of the mechanisms behind this phenomenon. As ctDNA migrates into the nucleus, genetic information is transferred. Cell targeting and ctDNA integration require ERVL, SINE or LINE DNA sequences. Chemically manufactured AluSp and MER11C sequences replicat ...[more]

PMID: 38783375

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Project description:Horizontal transfer of genetic material between complex organisms often involves transposable elements (TEs). For example, a DNA transposon mariner has been shown to undergo horizontal transfer between different orders of insects and between different phyla of animals. Here we report the discovery and characterization of an ITmD37D transposon, MJ1, in Anopheles sinensis. We show that some MJ1 elements in Aedes aegypti and An. sinensis contain intact open reading frames and share nearly 99% nucleotide identity over the entire transposon, which is unexpectedly high given that these two genera had diverged 145-200 million years ago. Chromosomal hybridization and TE-display showed that MJ1 copy number is low in An. sinensis. Among 24 mosquito species surveyed, MJ1 is only found in Ae. aegypti and the hyrcanus group of anopheline mosquitoes to which An. sinensis belongs. Phylogenetic analysis is consistent with horizontal transfer and provides the basis for inference of its timing and direction. Although report of horizontal transfer of DNA transposons between higher eukaryotes is accumulating, our analysis is one of a small number of cases in which horizontal transfer of nearly identical TEs among highly divergent species has been thoroughly investigated and strongly supported. Horizontal transfer involving mosquitoes is of particular interest because there are ongoing investigations of the possibility of spreading pathogen-resistant genes into mosquito populations to control malaria and other infectious diseases. The initial indication of horizontal transfer of MJ1 came from comparisons between a 0.4x coverage An. sinensis 454 sequence database and available TEs in mosquito genomes. Therefore we have shown that it is feasible to use low coverage sequencing to systematically uncover horizontal transfer events. Expanding such efforts across a wide range of species will generate novel insights into the relative frequency of horizontal transfer of different TEs and provide the evolutionary context of these lateral transfer events.

Dataset Information

Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.

Publications

Transposon DNA sequences facilitate the tissue-specific gene transfer of circulating tumor DNA between human cells.

Similar Datasets

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