A neochromosome is a

chromosome A chromosome is a package of DNA containing part or all of the genetic material of an organism. In most chromosomes, the very long thin DNA fibers are coated with nucleosome-forming packaging proteins; in eukaryotic cells, the most import ...

that is not normally found in nature.

Cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

-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 Genetic engineering techniques, technologies used to change the genet ...

techniques.

Cancer-associated neochromosomes

Cancer-associated neochromosomes are giant supernumerary chromosomes. They harbor the mutations that drive certain cancers (highly amplified copies of key

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

s, such as MDM2,

CDK4 Cyclin-dependent kinase 4 (CDK4), also known as cell division protein kinase 4, is an enzyme that is encoded by the ''CDK4'' gene in humans. CDK4 is a member of the cyclin-dependent kinase family, a group of serine/threonine kinases which regula ...

, HMGA2). They may be circular or linear chromosomes. They have functional

centromere The centromere links a pair of sister chromatids together during cell division. This constricted region of chromosome connects the sister chromatids, creating a short arm (p) and a long arm (q) on the chromatids. During mitosis, spindle fiber ...

s, and

telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see #Sequences, Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In ...

s 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 Liposarcomas are the most common subtype of soft tissue sarcomas, accounting for at least 20% of all sarcomas in adults. Soft tissue sarcomas are rare neoplasms with over 150 different histological subtypes or forms. Liposarcomas arise from the ...

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.Upton, G., Cook, I. (2008) ''Oxford Dictionary of Statistics'', OUP. . Inferential statistical analysis infers properties of ...

and

mathematical model A mathematical model is an abstract and concrete, abstract description of a concrete system using mathematics, mathematical concepts and language of mathematics, language. The process of developing a mathematical model is termed ''mathematical m ...

ling, the process of how neochromosomes initially form and evolve has been made clearer. Fragments of DNA produced following chromothriptic shattering of

chromosome 12 Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

undergo

DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

to form of a circular or ring chromosome. This undergoes hundreds of circular

breakage-fusion-bridge cycle Breakage-fusion-bridge (BFB) cycle (also breakage-rejoining-bridge cycle) is a mechanism of Chromosome instability, chromosomal instability, discovered by Barbara McClintock in the late 1930s. Mechanism The BFB cycle begins when the end region of ...

s, 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

s 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 {{Bioengineering-stub