Double minutes (DMs) are small fragments of extrachromosomal DNA, which have been observed in a large number of human tumors including breast, lung, ovary, colon, and most notably, neuroblastoma.
The most commonly proposed mechanism for DM formation is through chromothripsis, where up to hundreds of genomic arrangements occur in a single catastrophic event, and chromosome fragments which are not reintegrated join to create DMs.
[3] Another suggested mechanism is a multi-step evolutionary process, shown in the GLC1 cell line, in which a series of chromosomal mutation events within amplicons create subpopulations of DMs.
[4] Aside from these models, several studies suggest other processes for DM formation such as through the breakdown of a homogeneously staining region (HSR) following cell fusion,[5] through chromosomal breaks due to hypoxia induced activation of fragile sites,[6] or reduction in the level of DNA methylation.
[8] The “breakage-fusion-bridge” cycle, which describes an event where telomere loss causes the repeated joining and pulling apart of sister chromatids as cell division occurs, is a popular model to explain the amplification of intrachromosomal genes.
[12] Inducing the loss of extrachromosomally amplified genes in human tumor cells has been shown to reduce tumorigenicity, so the elimination of DMs or other ecDNA carrying oncogenes is one suggested avenue of cancer treatment research.