Novel insights into extrachromosomal DNA: redefining the onco-drivers of tumor progression
- PDF / 970,655 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 85 Downloads / 149 Views
(2020) 39:215
REVIEW
Open Access
Novel insights into extrachromosomal DNA: redefining the onco-drivers of tumor progression Xiang Gu1,2†, Jie Yu1,2†, Peiwei Chai1,2†, Shengfang Ge1,2* and Xianqun Fan1,2*
Abstract Extrachromosomal DNA (ecDNA), gene-encoding extrachromosomal particles of DNA, is often present in tumor cells. Recent studies have revealed that oncogene amplification via ecDNA is widespread across a diverse range of cancers. ecDNA is involved in increasing tumor heterogeneity, reverting tumor phenotypes, and enhancing gene expression and tumor resistance to chemotherapy, indicating that it plays a significant role in tumorigenesis. In this review, we summarize the characteristics and genesis of ecDNA, connect these characteristics with their concomitant influences on tumorigenesis, enumerate the oncogenes encoded by ecDNA in multiple cancers, elaborate the roles of ecDNA in tumor pathogenesis and progression, and propose the considerable research and therapeutic prospects of ecDNA in cancer. Keywords: Extrachromosomal DNA, Oncogene, Tumorigenesis
Background Genetic material guarantees the transmission of genetic information from parents to their offspring. With the exception of some viruses, DNA is the carrier of genetic material, which was first identified by Frederick Griffith in a Streptococcus pneumoniae transformation experiment [1–3]. DNA is present in a compacted and dynamic complex called chromatin in the cell nucleus. During the metaphase of cell division, chromatin organizes into highly condensed chromosomes [4]. DNA also exists in organelles including mitochondria and chloroplasts, which probably evolved from microorganisms such as αproteobacteria and cyanobacterium invading host cells and starting a symbiotic life form [5–8]. In addition, it has been reported that extrachromosomal particles of DNA exist, the size of which varies from dozens to millions of * Correspondence: [email protected]; [email protected] † Xiang Gu, Jie Yu and Peiwei Chai contributed equally to this work. 1 Department of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 20025, P. R. China Full list of author information is available at the end of the article
base pairs [9, 10]. These particles have been proved to be circular by biophysical methods and DNA sequencing. Verhaak et al. divided these particles into two types based on the size and resultant functions [11]. Small particles, which are called extrachromosomal circular DNA (eccDNA), are usually less than 1 kb; consequently, they are undetectable by light microscopy and lack full-length genes [12–14]. Investigations of eccDNA have revealed its association with aging, as eccDNA containing ribosomal DNA genes accumulates in old cells and contributes to the aging of yeast cells. The probable mechanism is described by the titration hypothesis, which indicates that the accumulated eccDNA might precipitate the components of replication and/or transcription elements, and eventually trigger the senescence and the
Data Loading...
