Engineered extrachromosomal oncogene amplifications promote tumorigenesis.

ABSTRACT: Focal gene amplifications are among the most common cancer-associated mutations¹ but have proven challenging to engineer in primary cells and model organisms. Here we describe a general strategy to engineer large (more than 1 Mbp) focal amplifications mediated by extrachromosomal DNAs (ecDNAs)² in a spatiotemporally controlled manner in cells and in mice. By coupling ecDNA formation with expression of selectable markers, we track the dynamics of ecDNA-containing cells under physiological conditions and in the presence of specific selective pressures. We also apply this approach to generate mice harbouring Cre-inducible Myc- and Mdm2-containing ecDNAs analogous to those occurring in human cancers. We show that the engineered ecDNAs spontaneously accumulate in primary c

SUBMITTER: Pradella D 

PROVIDER: S-EPMC11754114 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature