Modern biology of extrachromosomal DNA: A decade-long voyage of discovery  

作　　者：Qing-Lin Yang Yipeng Xie Kailiang Qiao Jun Yi Stanley Lim Sihan Wu 

机构地区：[1]Children’s Medical Center Research Institute,University of Texas Southwestern Medical Center,Dallas,TX,USA [2]Department of Molecular Biology,University of Texas Southwestern Medical Center,Dallas,TX,USA

出　　处：《Cell Research》2025年第1期11-22,共12页细胞研究(英文版)

基　　金：supported by the Cancer Prevention and Research Institute of Texas(CPRIT,RR210034);J.Y.S.L.is supported by the CPRIT Training Grant(RP210041);delivered as part of the eDyNAmiC team supported by the Cancer Grand Challenges partnership funded by Cancer Research UK(CGCATF-2021/100012 to P.S.M.,CGCATF-2021/100023 to S.W.);the National Cancer Institute(OT2CA278688 to P.S.M.,OT2CA278683 to S.W.).

摘　　要：Genomic instability is a hallmark of cancer and is a major driving force of tumorigenesis.A key manifestation of genomic instability is the formation of extrachromosomal DNAs(ecDNAs)—acentric,circular DNA molecules ranging from 50 kb to 5 Mb in size,distinct from chromosomes.Ontological studies have revealed that ecDNA serves as a carrier of oncogenes,immunoregulatory genes,and enhancers,capable of driving elevated transcription of its cargo genes and cancer heterogeneity,leading to rapid tumor evolution and therapy resistance.Although ecDNA was documented over half a century ago,the past decade has witnessed a surge in breakthrough discoveries about its biological functions.Here,we systematically review the modern biology of ecDNA uncovered over the last ten years,focusing on how discoveries during this pioneering stage have illuminated our understanding of ecDNAdriven transcription,heterogeneity,and cancer progression.Furthermore,we discuss ongoing efforts to target ecDNA as a novel approach to cancer therapy.This burgeoning field is entering a new phase,poised to reshape our knowledge of cancer biology and therapeutic strategies.

关 键 词：CHROMOSOMAL ELEVATED driving 

分 类 号：Q343.2[生物学—遗传学]