A neochromosome is a
chromosome that is not normally found in nature.
Cancer-associated neochromosomes are found in some cancer cells.
Neochromosomes have also been created using
genetic engineering
Genetic engineering, also called genetic modification or genetic manipulation, is the modification and manipulation of an organism's genes using technology. It is a set of technologies used to change the genetic makeup of cells, including t ...
techniques.
Cancer-associated neochromosomes
Cancer-associated neochromosomes are giant supernumerary chromosomes. They harbor the mutations that drive certain cancers (highly amplified copies of key
oncogenes, such as
MDM2,
CDK4
Cyclin-dependent kinase 4 also known as cell division protein kinase 4 is an enzyme that in humans is encoded by the ''CDK4'' gene. CDK4 is a member of the cyclin-dependent kinase family.
Function
The protein encoded by this gene is a member o ...
,
HMGA2). They may be circular or linear chromosomes. They have functional
centromeres, and
telomeres when linear. They are rare overall, being found in about 3% of cancers, but are common in certain rare cancers. For example, they are found in 90% of parosteal
osteosarcomas.
Neochromosomes from well- and de-differentiated
liposarcoma have been studied at high resolution by isolation (using flow sorting) and sequencing, as well as microscopy. They consist of hundreds of fragments of DNA, often derived from multiple normal chromosomes, stitched together randomly, and contain high levels of DNA amplification (~30-60 copies of some genes).
Using
statistical inference
Statistical inference is the process of using data analysis to infer properties of an underlying probability distribution, distribution of probability.Upton, G., Cook, I. (2008) ''Oxford Dictionary of Statistics'', OUP. . Inferential statistical ...
and
mathematical model
A mathematical model is a description of a system using mathematical concepts and language. The process of developing a mathematical model is termed mathematical modeling. Mathematical models are used in the natural sciences (such as physics, ...
ling, the process of how neochromosomes initially form and evolve has been made clearer. Fragments of DNA produced following
chromothriptic shattering of
chromosome 12 undergo
DNA repair to form of a circular or
ring chromosome. This undergoes hundreds of circular
breakage-fusion-bridge cycles, causing random amplification and deletion of DNA with selection for the amplification of key oncogenes. DNA from additional chromosomes is somehow added during this process. Erosion of
centromeres can lead to the formation of
neocentromeres or the capture of new native centromeres from other chromosomes. The process ends when the neochromosome forms a linear chromosome following the capture of telomeric caps, which can be chromothriptically derived.
References
Oncology
Genetic engineering
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