User:RG2022/Double minute

Lead/Article body
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, 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. [[Double minute]]

Characterized by their spherical nature, small size, and unique banding patterns, double minutes are "cytogenic equivalents of gene amplification." Double mutants are also the location of oncogenes, which are implicated in cancer, which makes them an area of interest for oncological therapies. Drug resistance genes including the dihydrofolate reductase (DHFR) gene are also located within double minutes.

Double minutes are particularly common in human epithelial, breast, ovarian, and lung tumors, and have been also found in hematological illnesses (though this is relatively rare). Studies have substantiated that the presence of double mutants is linked with poor prognoses and shorter life spans. However, if double mutants are the "sole chromosomal anomaly," then the prognosis is not as severe as that of a complex anomaly. Double minutes can be formed through the "deletion-plus-episome" model, more commonly known as simply the "episome" model, where portions of DNA are cut out from a whole chromosome and then amplified and circularized. The episome model was shown to be implicated in solid tumors, and was previously shown to be involved in leukemia, through a study of MYCN-amplified double minutes.

Extrachromosomal circular DNA (eccDNA), including double minutes, is shown have a greater increase of oncogenes during amplification than does chromosomal DNA and can be more stable than linear DNA, as seen by the cell-free eccDNA found in serum and plasma samples. These findings show that double mutants could rapidly evolve, resulting in the greater heterogeneity of tumors.

Expanding on the data above, I propose to continue reading studies having to do with the function of eccDNA in the formation of different cancers and tumors. I think it would be interest to focus on specific mutations within the double mutants that makes people more susceptible to certain kinds of cancers. I hope to summarize some of these findings.