Introduction
Name of the eccDNA | Size | Characteristic | Function |
---|---|---|---|
spcDNA | 100–10 kb | Homologous to repetitive chromosomal sequences; byproducts or intermediates of gene rearrangement | Initiation and enhancement of genomic instability |
telomeric circles | Integral multiples of 738 bp | Duplex or single-stranded molecule composed of telomeric repeats | Involved in the ALT of telomeres |
microDNA | 100–400 bp | Origin from regions with high GC content and exon density | Expressing functional small regulatory RNAs, including microRNAs and new si-like RNAs |
ecDNA | 1–3 Mb | Acentric, without telomere, containing full genes | Amplifying genes related to carcinogenesis and drug resistance |
The discovery of eccDNA
The biological characteristics of eccDNA
Small polydispersed circular DNA (spcDNA)
Telomeric circles (T-circles)
MicroDNA
Extrachromosomal DNA (ecDNA)
Main eccDNA research methods
How can a rough analysis of eccDNA be achieved?
Optical microscopy
Electron microscopy
Density gradient centrifugation
Assay of transposase-accessible chromatin with visualization (ATAC-see)
Fluorescence in situ hybridization (FISH)
Third-generation sequencing (TGS)
How to verify that eccDNA is circular?
Advanced eccDNA structure research methods
Circle-Sequencing (Circle-Seq)
Chromatin Immunoprecipitation Sequencing (ChIP-seq)
Circular chromosome conformation capture combined with high-throughput sequencing (4C-seq)
Proximity ligation-assisted ChIP-seq (PLAC-seq)
Assay for targeting accessible chromatin with high-throughput sequencing (ATAC-seq)
eccDNA analysis tools
AmpliconArchitect
AmpliconReconstructor
ecSeg
ViFi
ECdetect
Name | Characteristics | Website |
---|---|---|
AmpliconArchitect | It is a tool which can reconstruct the structure of focally amplified regions in a cancer sample using whole genome sequence short paired-end data | |
AmpliconReconstructor | It produces an ordering and orientation of graph segments, with fine-structure information from the breakpoint graph embedded into the large-scale reconstructions and as output, it reports large-scale reconstructions of fCNA amplicons | |
EcSeg | It is a tool used to quantify ecDNA in metaphase images. It also has an extension to analyze FISH probes | |
ViFi | It is a tool for detecting viral integration and fusion mRNA sequences from Next Generation Sequencing data. It uses both reference-based read mapping and a phylogenetic-based approach to identify viral reads and incorporates mappability scores of the reads to filter out false positive integration detection | |
ECdetect | It performs image pre-segmentation to distinguish between chromosomal and non-chromosomal structures, and calculates the interest (ROI) of the search area of ecDNA. The output of the software includes the original image covered with ecDNA detection, the number of ecDNA found, and their coordinates in the image | ECdetect will be available upon request |
The role of eccDNA in cancer
Cancer | Oncogene amplification via ecDNA | The connection between ecDNA and tumorigenesis |
---|---|---|
Neuroblastoma | n-myc | Remodeling the chromosomal genome, amplifying n-myc, promoting the expression of TERT and inhibiting the expression of DCLK1 |
Glioblastoma | EGFR, PDGFRA, ERBB2, KIT | Amplifying a variety of oncogenes, affecting tumor invasiveness, radiation resistance and drug resistance |
Colorectal carcinoma | DHFR | Amplifying DHFR to develop drug resistance |
Ovarian cancer | n-myc, EIF5A2 | Influencing the expression of ecDNA through MARS |
Breast cancer | HER2 | Amplifying HER2 to affect tumor drug resistance |