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Published on: May 6, 2009
Life of double minutes: generation, maintenance, and elimination
Mila Ilić1, Irene C Zaalberg1,2, Jonne A Raaijmakers1
1Division of Cell Biology, Oncode Institute, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
Abstract:
Advances in genome sequencing have revealed a type of extrachromosomal DNA, historically named double minutes (also referred to as ecDNA), to be common in a wide range of cancer types, but not in healthy tissues. These cancer-associated circular DNA molecules contain one or a few genes that are amplified when double minutes accumulate. Double minutes harbor oncogenes or drug resistance genes that contribute to tumor aggressiveness through copy number amplification in combination with favorable epigenetic properties. Unequal distribution of double minutes over daughter cells contributes to intratumoral heterogeneity, thereby increasing tumor adaptability. In this review, we discuss various models delineating the mechanism of generation of double minutes. Furthermore, we highlight how double minutes are maintained, how they evolve, and discuss possible mechanisms driving their elimination.
Insights
Extrachromosomal DNA, known as double minutes (ecDNA), are prevalent in cancers but absent in healthy cells. These circular DNA elements amplify oncogenes, driving tumor aggressiveness and heterogeneity.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Oncology
Background:
- Extrachromosomal DNA (ecDNA), including double minutes, are frequently detected in various cancers.
- Unlike normal cells, cancer cells harbor ecDNA, which contains amplified oncogenes or drug resistance genes.
- ecDNA contributes to tumor aggressiveness and adaptability through gene amplification and epigenetic modifications.
Purpose of the Study:
- To review current understanding of double minutes (ecDNA) in cancer.
- To elucidate the mechanisms of ecDNA generation, maintenance, and evolution.
- To explore potential mechanisms for ecDNA elimination.
Main Methods:
- Review of existing literature on ecDNA and double minutes.
- Analysis of genomic sequencing data identifying ecDNA in cancer.
- Discussion of proposed models for ecDNA formation and regulation.
Main Results:
- Double minutes (ecDNA) are common in diverse cancer types, absent in healthy tissues.
- ecDNA harbors amplified oncogenes and drug resistance genes, promoting tumor progression.
- Unequal segregation of ecDNA leads to intratumoral heterogeneity and increased adaptability.
Conclusions:
- Double minutes (ecDNA) play a critical role in cancer development and progression.
- Understanding ecDNA dynamics is crucial for developing targeted cancer therapies.
- Further research is needed to explore therapeutic strategies targeting ecDNA elimination.
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