Abstract
Abstract Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA poses one of the greatest challenges for cancer patients, affecting children and adults and women and men, with a wide variety of cancer types. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. ecDNA, because of its non-chromosomal inheritance, drives high-copy number oncogene amplification and enables tumors to evolve their genomes rapidly, contributing to treatment resistance and shorter survival for patients. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription. In this talk, I will discuss recent collaborative discoveries that highlight how the higher order, spatial organization of ecDNA, and its mechanism of inheritance, contributes to aggressive tumorigenesis, accelerated evolution, and treatment resistance. Citation Format: Paul S. Mischel. Extrachromosomal DNA (ecDNA): Cancer's dynamic circular genome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY03-02.
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