《生命科学》 2023, 35(6): 824-832

基于高通量测序技术对染色体外环状DNA研究的最新进展

郭志涛^1,2 , 武慧慧^1,2 , 耿淑慧^1,2 , 陈　晨^1,2 , 孟祥宁^1,2 , 孙文靖^1,2 , 朱　静^1,2,*

¹哈尔滨医科大学医学遗传学研究室，哈尔滨 150081 ²中国遗传资源保护与 疾病防控教育部重点实验室(哈尔滨医科大学)，哈尔滨 150081

摘　要：

染色体外环状DNA (extrachromosomal circular DNA, eccDNA) 是一种真核生物染色体外的闭合环状DNA 结构，长度和染色体起源具有较高异质性。eccDNA 这一名称目前主要指大小在数百kb 以内的小分子染色体外环状DNA，包括microDNA、小多分散环状DNA (small polydispersed circular DNA, spcDNA) 以及其他未分类的小分子eccDNA 等。高通量测序技术(high-throughput sequencing, HTS) 是一种可以同时对百万条DNA 分子进行序列测定的技术，又名新一代测序技术(next generation sequencing, NGS)，具有高通量、高灵敏度、高准确度等优势。近年来高通量测序结合生物信息学分析技术不仅在揭示eccDNA 染色体起源、分子结构、发生机制和潜在功能以及循环系统中的eccDNA 分子特征研究等方面发挥了重要作用，而且推动了eccDNA 在甲基化等表观遗传学方面的研究。生物信息学软件的发展和eccDNA 分析算法的开发也对其研究提供了重要帮助。血浆以及尿液等液体活检常用体液样本中也鉴定出eccDNA 的广泛存在，并且表现出与组织、生理状态以及疾病相关的生物学特征。eccDNA 可能是重要的液体活检候选标志物。本综述旨在阐述利用高通量测序技术在研究eccDNA 的结构、发生机制和功能上取得的最新成果，并讨论eccDNA 在液体活检等方面的潜在应用。

通讯作者：朱　静 , Email:zhuj@hrbmu.edu.cn

Research advances of extrachromosomal circular DNAs (eccDNAs) using next generation sequencing technology

GUO Zhi-Tao^1,2 , WU Hui-Hui^1,2 , GENG Shu-Hui^1,2 , CHEN Chen^1,2 , MENG Xiang-Ning^1,2 , SUN Wen-Jing^1,2 , ZHU Jing^1,2,*

¹Laboratory of Medical Genetics, Harbin Medical University, Harbin 150081, China ²Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin 150081, China

Abstract:

Extrachromosomal circular DNA (eccDNA) is a closed circular DNA structure outside the chromosomes of eukaryotes. The sizes and chromosome origins of eccDNA are highly heterogeneous. At present, the name eccDNA mainly refers to small circular DNA sized less than housands of kilo bases, which includes microDNA, small polydispersed circular DNA (spcDNA) and other unclassified eccDNA molecules. High-throughput sequencing (HTS) also known as next generation sequencing (NGS), is a technology that can simultaneously sequence millions of DNA molecules, with the advantages of high throughput, high sensitivity and high accuracy. In recent years, high-throughput sequencing combined with bioinformatics analysis methods has greatly promoted research of the origin, molecular structure, genetic mechanism and potential function of eccDNA, the research on the molecular characteristics of eccDNA in the circulating system, as well as the research on epigenetics such as methylation of eccDNA. The development of bioinformatic software and eccDNA analysis algorithm also provides important help for eccDNA research. EccDNAs have also been widely identified in plasma, urine and other body fluid samples, which are commonly used for liquid biopsy, and show biological characteristics related to tissue, physiological status and diseases. EccDNA may become important biomarkers for liquid biopsy. This review aims to discuss the latest research progress of the structure, mechanism and function of eccDNAs by using highthroughput sequencing technologies and the potential clinical application of eccDNAs in liquid biopsy.

Communication Author：ZHU Jing , Email:zhuj@hrbmu.edu.cn