Life of double minutes: generation, maintenance, and elimination

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.

Automated summary

Advances in genome sequencing have revealed the presence of double minutes, a type of extrachromosomal DNA, in various types of cancer. These circular DNA molecules contain amplified oncogenes or drug resistance genes and contribute to tumor aggressiveness. Unequal distribution of double minutes increases intratumoral heterogeneity. This review discusses the generation, maintenance, evolution, and potential mechanisms of elimination of double minutes.