ecDNAs are fragments of extrachromosomal DNA, which are observed in tumors

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There are many forms of DNA, in Eukariotic cells that are not in replicating phases they are long linear structures, but in mitochondria they are circular. In bacteria DNA is also circular. Plasmids, another form of DNA is also circular.

While the chromosomes are big and contain all the essential genetic information for living under normal conditions, plasmids usually are very small and contain only additional genes that may be useful in certain situations or conditions.

Plasmids are capable of replicating autonomously within a suitable host, they are transmitted from one bacterium to another (even of another species), this host-to-host transfer of genetic material is one mechanism of horizontal gene transfer

Several forms of ADN

Since the 1970' we know that plasmid like DNA exist also organisms and they are involved in cancer. ecDNAs are fragments of extrachromosomal DNA, which were originally observed in a large number of human tumors and most notably, neuroblastoma.

In contrast to bacterial plasmids or mitochondrial DNA, ecDNA are chromatinized, containing high levels of active histone marks, but a paucity of repressive histone marks. The ecDNA chromatin architecture lacks the higher-order compaction that is present on chromosomal DNA and is among the most accessible DNA in the entire cancer genome.

For their new study, Paul Mischel and colleagues shown that ecDNA are wound around protein cores in a fashion that permits a far greater level of accessibility to the transcriptional machinery than occurs on chromosomes. As a result of this unique architecture, along with the very high number of ecDNA particles inside a tumor cell, oncogenes that are amplified on ecDNA are amongst the most highly transcribed genes in a tumor. Mischel and teammates have constructed circular maps of ecDNA which they say might prove valuable in guiding drug discovery.

The study’s co-senior author, UCSD's Paul Mischel, Ph.D., has founded a biotech called Boundless Bio to advance treatments aimed at ecDNA. In September, the startup emerged from stealth mode with $46 million in series A funding led by Arch Venture Partners and City Hill Ventures.


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