A neochromosome is a

chromosome A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

that is not normally found in nature.

Cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

-associated neochromosomes are found in some cancer cells. Neochromosomes have also been created using genetic engineering 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,

HMGA2 High-mobility group AT-hook 2, also known as HMGA2, is a protein that, in humans, is encoded by the ''HMGA2'' gene. Function This gene encodes a protein that belongs to the non-histone chromosomal high-mobility group (HMG) protein family. HMG ...

). 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 fibers ...

s, and

telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...

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 pr ...

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 and mathematical modelling, 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 to ...

undergo

DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...

to form of a circular or

ring chromosome A ring chromosome is an aberrant chromosome whose ends have fused together to form a ring. Ring chromosomes were first discovered by Lilian Vaughan Morgan in 1926. A ring chromosome is denoted by the symbol ''r'' in human genetics and ''R'' in '' ...

. This undergoes hundreds of circular

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

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

neocentromere Neocentromeres are new centromeres that form at a place on the chromosome that is usually not centromeric. They typically arise due to disruption of the normal centromere. These neocentromeres should not be confused with “knobs”, which were al ...

s 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 {{oncology-stub