🧪1/ 🚨New paper on ecDNAs from our lab!
We reveal a strategy to engineer extrachromosomal DNA (ecDNA) amplifications in cells & mice. Let's dive in! Let’s dive in! 🧵👇
https://www.nature.com/articles/s41586-024-08318-8
We reveal a strategy to engineer extrachromosomal DNA (ecDNA) amplifications in cells & mice. Let's dive in! Let’s dive in! 🧵👇
https://www.nature.com/articles/s41586-024-08318-8
Comments
ecDNAs had been known since the 60s (they were called "Double Minutes"). They are large circular DNA fragments found in some of the most aggressive forms of cancers. They amplify oncogenes, boost gene expression, facilitate tumor evolution, and increase resistance to therapy.
In contrast to most other classes of mutations, focal gene amplifications like ecDNAs have proven difficult to model in primary cells or animals. This study overcomes this limitation. 🔬
For the in vitro studies the loxP sites were inserted as part of two larger "circularization cassettes". Upon circularization a drug resistance and a GFP transgene are expressed from the ecDNA while an mScarlett reporter is encoded from the 'scar' on the chromosome.
To test this strategy, we engineered the formation of a 1.5Mbp ecDNA encompassing the MDM2 locus (as well as a bunch of other genes) in HCT116 cells, which are otherwise diploid and chromosomally stable.