Exploring the Potential of Extrachromosomal DNA As a Novel Oncogenic Driver

Overview

Journal Sci China Life Sci

Specialties Biology
Science

Date 2024 Sep 30

PMID 39349791

Authors

Huanbo Zhu

Longtao Huangfu

Junbing Chen

Jiafu Ji

Xiaofang Xing

Affiliations

Soon will be listed here.

Abstract

Extrachromosomal DNA (ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity, oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

References

Aguilera P, Dubarry M, Hardy J, Lisby M, Simon M, Geli V . Telomeric C-circles localize at nuclear pore complexes in Saccharomyces cerevisiae. EMBO J. 2022; 41(6):e108736. PMC: 8922269. DOI: 10.15252/embj.2021108736. View

Ashique S, Upadhyay A, Garg A, Mishra N, Hussain A, Negi P . Impact of ecDNA: A mechanism that directs tumorigenesis in cancer drug Resistance-A review. Chem Biol Interact. 2022; 363:110000. DOI: 10.1016/j.cbi.2022.110000. View

Buenrostro J, Giresi P, Zaba L, Chang H, Greenleaf W . Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat Methods. 2013; 10(12):1213-8. PMC: 3959825. DOI: 10.1038/nmeth.2688. View

Burrell R, McGranahan N, Bartek J, Swanton C . The causes and consequences of genetic heterogeneity in cancer evolution. Nature. 2013; 501(7467):338-45. DOI: 10.1038/nature12625. View

Calcinotto A, Kohli J, Zagato E, Pellegrini L, Demaria M, Alimonti A . Cellular Senescence: Aging, Cancer, and Injury. Physiol Rev. 2019; 99(2):1047-1078. DOI: 10.1152/physrev.00020.2018. View

Carroll S, DeRose M, Gaudray P, Moore C, Von Hoff D, Wahl G . Double minute chromosomes can be produced from precursors derived from a chromosomal deletion. Mol Cell Biol. 1988; 8(4):1525-33. PMC: 363312. DOI: 10.1128/mcb.8.4.1525-1533.1988. View

Carroll S, Gaudray P, De Rose M, Emery J, Meinkoth J, Nakkim E . Characterization of an episome produced in hamster cells that amplify a transfected CAD gene at high frequency: functional evidence for a mammalian replication origin. Mol Cell Biol. 1987; 7(5):1740-50. PMC: 365275. DOI: 10.1128/mcb.7.5.1740-1750.1987. View

Cohen S, Regev A, Lavi S . Small polydispersed circular DNA (spcDNA) in human cells: association with genomic instability. Oncogene. 1997; 14(8):977-85. DOI: 10.1038/sj.onc.1200917. View

Cortes-Ciriano I, Lee J, Xi R, Jain D, Jung Y, Yang L . Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing. Nat Genet. 2020; 52(3):331-341. PMC: 7058534. DOI: 10.1038/s41588-019-0576-7. View

10.

Dagogo-Jack I, Shaw A . Tumour heterogeneity and resistance to cancer therapies. Nat Rev Clin Oncol. 2017; 15(2):81-94. DOI: 10.1038/nrclinonc.2017.166. View

11.

deCarvalho A, Kim H, Poisson L, Winn M, Mueller C, Cherba D . Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma. Nat Genet. 2018; 50(5):708-717. PMC: 5934307. DOI: 10.1038/s41588-018-0105-0. View

12.

Deng X, Zhang L, Zhang Y, Yan Y, Xu Z, Dong S . Double minute chromosomes in mouse methotrexate-resistant cells studied by atomic force microscopy. Biochem Biophys Res Commun. 2006; 346(4):1228-33. DOI: 10.1016/j.bbrc.2006.06.041. View

13.

Deshpande V, Luebeck J, Nguyen N, Bakhtiari M, Turner K, Schwab R . Exploring the landscape of focal amplifications in cancer using AmpliconArchitect. Nat Commun. 2019; 10(1):392. PMC: 6344493. DOI: 10.1038/s41467-018-08200-y. View

14.

Dillon L, Kumar P, Shibata Y, Wang Y, Willcox S, Griffith J . Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity. Cell Rep. 2015; 11(11):1749-59. PMC: 4481157. DOI: 10.1016/j.celrep.2015.05.020. View

15.

Disis M . Immune regulation of cancer. J Clin Oncol. 2010; 28(29):4531-8. PMC: 3041789. DOI: 10.1200/JCO.2009.27.2146. View

16.

Drews R, Hernando B, Tarabichi M, Haase K, Lesluyes T, Smith P . A pan-cancer compendium of chromosomal instability. Nature. 2022; 606(7916):976-983. PMC: 7613102. DOI: 10.1038/s41586-022-04789-9. View

17.

Gall J, Pardue M . Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc Natl Acad Sci U S A. 1969; 63(2):378-83. PMC: 223575. DOI: 10.1073/pnas.63.2.378. View

18.

Gisselsson D, Pettersson L, Hoglund M, Heidenblad M, Gorunova L, Wiegant J . Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity. Proc Natl Acad Sci U S A. 2000; 97(10):5357-62. PMC: 25833. DOI: 10.1073/pnas.090013497. View

19.

Guo J, Zhang Z, Li Q, Chang X, Liu X . TeCD: The eccDNA Collection Database for extrachromosomal circular DNA. BMC Genomics. 2023; 24(1):47. PMC: 9881285. DOI: 10.1186/s12864-023-09135-5. View

20.

He S, Xia C, Li H, Cao M, Yang F, Yan X . Cancer profiles in China and comparisons with the USA: a comprehensive analysis in the incidence, mortality, survival, staging, and attribution to risk factors. Sci China Life Sci. 2023; 67(1):122-131. DOI: 10.1007/s11427-023-2423-1. View