Background
Characteristics of ecDNA
chrDNA | ecDNA | Function of ecDNA based on the difference | Outcome in tumorigenesis | Reference | |
---|---|---|---|---|---|
Structure | Circular | Linear | High chromatin accessibility and ultra-long-range chromatin contact | High levels of oncogene transcription and expression | [19] |
Centromere | Centric | Acentric | Uneven segregation during cell division | Increased intratumoral heterogeneity and enhanced fitness to changing environments | |
Stability | Stable | Unstable | Eliminable via micronucleus formation | Tumor phenotype reversion |
ecDNA is acentric with uneven segregation at cell division
The resultant heterogeneity in cancer with ecDNA
ecDNA can be eliminated by micronucleus formation
The resultant tumor reversion in cancer with ecDNA
ecDNA is circular with highly accessible chromatin and ultra-long-range chromatin contacts
The resultant distal chromatin contact in cancer with ecDNA
Genesis of ecDNA
Model | Mechanism | Reference |
---|---|---|
Episome | Replication bubble drop from the chromosome to produce an episome and then the episome replicates and recombines to form ecDNA. | |
Translocation-excision-deletion-amplification | Two chromosomes translocate with subsequent excision and deletion at the regions neighboring translocation breakpoints, and then the separate fragments amplify and circularize to form ecDNA. | [56] |
Chromothripsis | Chromosomes are isolated into fragments through an error in cell segregation, and the fragments connect randomly to produce ecDNA. | |
A multistep evolutionary process | The single-chromosome ancestral episomes undergo a series of discrete mutation events, including recombinations, deletions and duplications to produce various ecDNAs. |
Episome in ecDNA
Translocation-excision-deletion-amplification in ecDNA
Chromothripsis in ecDNA
A multistep evolutionary process in ecDNA
ecDNA in cancer
Cancer | Oncogene amplification via ecDNA | The connection between ecDNA and tumorigenesis | Reference |
---|---|---|---|
Neuroblastoma | MYCN | ecDNA remodels the chromosomal genome and affects chromosomal gene expression, including oncogenes and tumor suppressors | [64] |
Glioblastoma | MYC, EGFR, PDGFRα, ERBB2, CDK4, MDM2 | The oncogenes residing on ecDNA are dynamically regulated to evade therapy | |
Colon cancer | DHFR | Tumor cells upregulate DHFR amplification via ecDNA to develop drug resistance | |
Ovarian cancer | MYCN, EIF5AR | The noncoding regions of ecDNA may regulate gene expression | [69] |
Breast cancer | HER2 | Dynamic regulation of oncogenes residing on ecDNA is not supported by HER2 | [70] |