Double minute

Double minutes 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. They are a manifestation of gene amplification as a result of chromothripsis,^[1] during the development of tumors, which give the cells selective advantages for growth and survival. This selective advantage is as a result of double minutes frequently harboring amplified oncogenes and genes involved in drug resistance. Double minutes, like actual chromosomes, are composed of chromatin and replicate in the nucleus of the cell during cell division. Unlike typical chromosomes, they are composed of circular fragments of DNA, up to only a few million base pairs in size and contain no centromere or telomere. Further to this, they often lack key regulatory elements, allowing genes to be constitutively expressed. Recently, some research groups are re-branding double minutes as ecDNA.^[2]

References[]

^ Stephens PJ, Greenman CD, Fu B, et al. (2011). "Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development". Cell. 144 (1): 27–40. doi:10.1016/j.cell.2010.11.055. PMC 3065307. PMID 21215367.
^ Wu, Sihan; Turner, Kristen M.; Nguyen, Nam; Raviram, Ramya; Erb, Marcella; Santini, Jennifer; Luebeck, Jens; Rajkumar, Utkrisht; Diao, Yarui; Li, Bin; Zhang, Wenjing (November 2019). "Circular ecDNA promotes accessible chromatin and high oncogene expression". Nature. 575 (7784): 699–703. Bibcode:2019Natur.575..699W. doi:10.1038/s41586-019-1763-5. ISSN 1476-4687. PMC 7094777. PMID 31748743.

Baskin, F; Rosenberg, RN; Dev, V (June 1981). "Correlation of double-minute chromosomes with unstable multidrug cross-resistance in uptake mutants of neuroblastoma cells". Proc Natl Acad Sci USA. 78 (6): 3654–3658. Bibcode:1981PNAS...78.3654B. doi:10.1073/pnas.78.6.3654. PMC 319629. PMID 6943568. Free full-text.
Barker PE (February 1982). "Double minutes in human tumor cells". Cancer Genetics and Cytogenetics. 5 (1): 81–94. doi:10.1016/0165-4608(82)90043-7. PMID 6175392.
Masters, J; Keeley, B; Gay, H; Attardi, G (1982). "Variable content of double minute chromosomes is not correlated with degree of phenotype instability in methotrexate-resistant human cell lines". Mol Cell Biol. 2 (5): 498–507. doi:10.1128/mcb.2.5.498. PMC 369819. PMID 7110138. Free full-text.

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[Stephens2011-1] Stephens PJ, Greenman CD, Fu B, et al. (2011). "Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development". Cell. 144 (1): 27–40. doi:10.1016/j.cell.2010.11.055. PMC 3065307. PMID 21215367.

[2] Wu, Sihan; Turner, Kristen M.; Nguyen, Nam; Raviram, Ramya; Erb, Marcella; Santini, Jennifer; Luebeck, Jens; Rajkumar, Utkrisht; Diao, Yarui; Li, Bin; Zhang, Wenjing (November 2019). "Circular ecDNA promotes accessible chromatin and high oncogene expression". Nature. 575 (7784): 699–703. Bibcode:2019Natur.575..699W. doi:10.1038/s41586-019-1763-5. ISSN 1476-4687. PMC 7094777. PMID 31748743.

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Double minute

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