New findings: extracellular DNA can express carcinogenic genes in large quantities and promote the rapid growth of cancer cells

Yesterday, we reported a massive study in the journal Nature A team from Stanford University and the University of California, San Diego, found that extra chromosomal DNA (ecdna) can express a large number of carcinogenic genes and promote the rapid growth of cancer cells Only a day later, the top academic journal Cell published another important study on ecdna This time, scientists leading the study came from UCSD and Case Western Reserve University They found that in glioblastoma, a malignant brain tumor, there is also a ring of ecdna It has not only the EGFR gene that promotes cancer development, but also many sequences that enhance it What's more surprising is that some sequences were not originally around the EGFR gene They are more like cancer cells from all parts of the genome "pumping" out, specifically to strengthen oncogenes! How is this research done? That starts with oncogenes Scientists have long noticed that the number of copies of oncogenes in cancer cells increases Sometimes, the number of abnormal increase is not only the coding sequence, but also some non coding DNA The role of these noncoding DNA in cancer cells has always been a mystery In this study, the scientists decided to explore the non coding DNA, and their research object was glioblastoma In this extremely dangerous brain tumor, we can often observe the over activity of EGFR gene When there are a large number of copies of EGFR genes in tumors, these oncogenes tend to form a circular ecdna structure As the name suggests, it's a DNA that's independent of chromosomes and looks like plasmid DNA in bacteria ▲ in the cells of glioblastoma, scientists observed the EGFR gene (red) stained in vitro (photo journey of Case Western Reserve) In this kind of circular DNA, EGFR gene is not the only one On the contrary, in some tumor samples, they found that there are many enhancer sequences or other regulatory elements near the EGFR gene It is easy to understand that some of these regulatory elements are located close to EGFR But it's frightening to think that some other regulatory elements seem to have been snatched from unrelated parts of the genome! To understand the function of these regulatory elements, scientists used CRISPR gene editing technology to silence them one by one And the results are not optimistic - almost every regulatory element promotes tumor growth "It's like the oncogene grabs' switches' from all over the genome to maximize its expression." Professor Peter scacheri, one of the study's co authors, said ▲ illustration of this study (picture source: reference [1]) Later, scientists found that this phenomenon is not limited to EGFR gene, but also in glioblastoma By consulting the public cancer genetics database, there are similar phenomena in many cancer types The most common are myc gene in medulloblastoma and MYCN gene in neuroblastoma Moreover, even if two types of tumors are driven by the same oncogene, the regulatory elements behind these oncogenes are likely to be different To this end, the researchers pointed out that in the past, we paid too much attention to the oncogene itself, but ignored the enhancer of the oncogene In the future, we should pay more attention to cancer treatment At the same time of targeting oncogenes, we also need to consider how to turn off the switch to activate these oncogenes "It's not just the phenomenon observed in the lab, it's the information that really helps the patient." Professor Jeremy n rich, another corresponding author, said reference material: [1] Andrew R Morton et al., (2019), Functional Enhancers Shape Extrachromosomal Oncogene Amplifications, Cell, DOI: https://doi.org/10.1016/j.cell.2019.10.039