摘要
染色体碎裂化是指在一次细胞灾难性事件当中,染色体片段被全部打碎,然后这些片段以另一种顺序重组。经过染色体碎裂化的细胞一般会死亡,仅极少数细胞幸存下来,可能是由于大规模基因组重排让细胞有转化为癌细胞的趋势。染色体碎裂化导致的后果包括癌基因的扩增、抑癌基因的丢失以及融合基因的形成等。在染色体碎裂化的过程中,那些未参与重组的碎裂片段,一些会丢失,另一些则作为染色体外DNA(Extrachromosomal DNA,ecDNA)持续存在。这些ecDNA中的一些促进了癌细胞的生长,并能形成微小尺寸染色体,称为双微体。目前染色体碎裂化检测技术可分为常规检测技术与高通量基因测序检测技术。常规检测技术有荧光原位杂交、外周淋巴细胞核型分析和染色体微阵列技术,高通量基因测序检测技术有下一代测序技术以及长读长基因测序技术。在分析染色体碎裂化技术上,长读长基因测序技术具有更大的优势,它不仅可准确检测出染色体碎裂的断点位置,还可对破碎的片段进行定向识别与排序,检测出复杂重排位点,弥补短读长基因测序和常规检测技术上的缺陷。本文主要对染色体碎裂化在促进肿瘤进展和耐药中的作用以及当前相关检测技术的优缺点进行综述。
Chromothripsis refers to that chromosome fragments were all broken and then tens to hundreds of genomes rearranged in a single catastrophic event.After chromothripsis,cells generally die,and only a few cells can survive.It may be because the large-scale rearrangement of the genome makes the cells tend to turn into cancer cells.This may be related to the consequences of chromothripsis,including the amplification of oncogenes,the loss of tumor suppressor genes and the formation of fusion genes.In the process of chromothripsis,some fragments that are not involved in rearrangement will be lost,while others continue to exist as extrachromosomal DNA(ecDNA).Some of ecDNA promote the growth of cancer cells and form tiny chromosomes called double-minute chromosome.Chromothripsis detection technology can be divided into routine detection technology and high-throughput gene sequencing detection technology.Routine detection techniques include fluorescence in situ hybridization(FISH),peripheral lymphocyte karyotype analysis and chromosomal microarray analysis(CMA).High-throughput gene sequencing detection technologies include next generation sequencing(NGS)and long-read gene sequencing.In the analysis of chromothripsis technology,long-read sequencing technology has more advantages.It can accurately detect not only the breakpoint location of chromothripsis,but also directional identification and sequencing of broken fragments,and detect complex rearrangement sites,which makes up for many defects in short-read gene sequencing and conventional detection technology.This review will summarize the role of chromothripsis in tumorigenesis and drug resistance,as well as the advantages and disadvantages of current related detection technologies.
作者
李颖
罗娟娟
徐天菡
万绍贵
LI Ying;LUO Juan-juan;XU Tian-han;WANG Shao-gui(School of Basic Medicine,Gannan Medical University;Center for Molecular Pathology,School of Basic Medicine,Gannan Medical University,Ganzhou,Jiangxi 341000)
出处
《赣南医学院学报》
2022年第4期331-337,共7页
JOURNAL OF GANNAN MEDICAL UNIVERSITY
基金
江西省科技创新杰出青年人才资助计划项目(20192BCBL23017)。
