Hyperactive nuclear loops

A study led by Ludwig San Diego’s Paul Mischel and Bing Ren with Ludwig Stanford’s Howard Chang took a deep dive into how extrachromosomal DNA (ecDNA) drives tumor growth, heterogeneity and drug resistance. Circles of DNA that exist outside chromosomes and encode multiple copies of growth-driving genes, ecDNAs are almost exclusively found in cancer cells. Previous work in Paul’s lab uncovered the phenomenon and revealed that ecDNA plays a key role in tumor progression and cellular heterogeneity across a large variety of cancers. In their most recent study, the team investigated the link between the molecular structure and gene expression patterns of ecDNAs using a variety of genomic analysis tools. They reported in Nature in November that though ecDNA is wound tightly around protein cores, it is structured in a manner that makes its cancer-driving genes highly accessible and prone to extraordinarily high levels of expression. The pitched expression of oncogenes in turn helps tumor cells evolve more quickly and respond more nimbly to changing environments and threats like cancer therapy.

This article appeared in the April 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).


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