在癌症中，复杂的基因组重排和其他结构变化，包括环状染色体外来源的癌基因（ecDNA）元素扩增，推动了肿瘤的形成和进展。 ecDNA是一种尤其具有挑战性的结构变化。它通过解除癌基因对染色体的约束，提高癌基因复制数，推动肿瘤内遗传异质性，促进快速肿瘤进化，并导致治疗耐药性。 ecDNA产生的DNA形状和细胞核的深刻变化，通过催化某些不会发生在染色体上的新类型的调控相互作用，改变了肿瘤的转录景观。目前用于探究癌症基因组的工具套件非常适合解读序列，但是具有有限的能力来解决ecDNA所产生的DNA结构和动力学的复杂变化。在这里，我们回顾了解决ecDNA形态和功能的挑战，并讨论了解密ecDNA架构和空间组织的新兴工具套件，包括迄今为止有关这种形态变化如何改变肿瘤发展、进展和药物耐药性的发现。

In cancer, complex genome rearrangements and other structural alterations, including the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements, drive the formation and progression of tumors. ecDNA is a particularly challenging structural alteration. By untethering oncogenes from chromosomal constraints, it elevates oncogene copy number, drives intratumoral genetic heterogeneity, promotes rapid tumor evolution, and results in treatment resistance. The profound changes in DNA shape and nuclear architecture generated by ecDNA alter the transcriptional landscape of tumors by catalyzing new types of regulatory interactions that do not occur on chromosomes. The current suite of tools for interrogating cancer genomes is well suited for deciphering sequence but has limited ability to resolve the complex changes in DNA structure and dynamics that ecDNA generates. Here, we review the challenges of resolving ecDNA form and function and discuss the emerging tool kit for deciphering ecDNA architecture and spatial organization, including what has been learned to date about how this dramatic change in shape alters tumor development, progression, and drug resistance.