The term neochromosome describes certain kinds of chromosome not normally found in nature.
Cancer-associated neochromosomes
editCancer-associated neochromosomes (CaNCs) are large, supernumerary chromosomes most commonly seen in mesenchymal tumors (sarcomas), especially osteosarcoma, dermatofibrosarcoma protuberans, and well-differentiated and de-differentiated liposarcomas (WD/DDLPS). They occur in ring- and "giant rod"-shaped forms.[1]
The DNA sequence that makes up CaNCs has its origin in many different wild type chromosomes, and can be highly amplified. CaNCs often possess functional centromeres and telomeres. These characteristics distinguish CaNCs from constitutional ring chromosomes -- as in ring chromosome 14 and ring chromosome 20 syndrome -- and other forms of chromosomal rearrangement and abnormality in cancer, like double minutes.
CaNCs have been most closely studied in well-differentiated and de-differentiated liposarcomas. One or more CaNCs are seen in 80% of WDLPS samples; the oncogene-rich locus 12q13-15, containing MDM2 and CDK4, is usually highly amplified.[1] It is believed that these CaNCs initially arise as circular structures due to a chromothriptic event involving (at least) chromosome 12. Following this, breakage-fusion-bridge cycles are thought to amplify, rearrange, and delete the CaNC's genetic material. Under selection and over many generations, oncogenes are amplified; sequence from other chromosomes may be incorporated as well. Eventually, after developing or acquiring functional neocentromeres[2] and telomeres, these neochromosomes stabilize in linear form.[3]
Synthetic neochromosomes
editNeochromosomes have also been created using genetic engineering techniques.[4][5]
References
edit- ^ a b Garsed, D. W.; Holloway, A. J.; Thomas, D. M. (2009). "Cancer-associated neochromosomes: A novel mechanism of oncogenesis". BioEssays. 31 (11): 1191–200. doi:10.1002/bies.200800208. PMID 19795405.
- ^ Amor, D.; Choo, K. (2002). "Neocentromeres: Role in Human Disease, Evolution, and Centromere Study". The American Journal of Human Genetics. 71 (4): 695. doi:10.1086/342730.
- ^ Garsed, D. W.; Marshall, O. J.; Corbin, V. D. A.; Hsu, A.; Di Stefano, L.; Schröder, J.; Li, J.; Feng, Z. P.; Kim, B. W.; Kowarsky, M.; Lansdell, B.; Brookwell, R.; Myklebost, O.; Meza-Zepeda, L.; Holloway, A. J.; Pedeutour, F.; Choo, K. H. A.; Damore, M. A.; Deans, A. J.; Papenfuss, A. T.; Thomas, D. M. (2014). "The Architecture and Evolution of Cancer Neochromosomes". Cancer Cell. 26 (5): 653. doi:10.1016/j.ccell.2014.09.010.
{{cite journal}}: no-break space character in|first17=at position 7 (help); no-break space character in|last5=at position 3 (help) - ^ Callaway, E. (2014). "First synthetic yeast chromosome revealed". Nature. doi:10.1038/nature.2014.14941.
- ^ Annaluru, N.; Muller, H.; Mitchell, L. A.; Ramalingam, S.; Stracquadanio, G.; Richardson, S. M.; Dymond, J. S.; Kuang, Z.; Scheifele, L. Z.; Cooper, E. M.; Cai, Y.; Zeller, K.; Agmon, N.; Han, J. S.; Hadjithomas, M.; Tullman, J.; Caravelli, K.; Cirelli, K.; Guo, Z.; London, V.; Yeluru, A.; Murugan, S.; Kandavelou, K.; Agier, N.; Fischer, G.; Yang, K.; Martin, J. A.; Bilgel, M.; Bohutskyi, P.; et al. (2014). "Total Synthesis of a Functional Designer Eukaryotic Chromosome". Science. 344 (6179): 55. doi:10.1126/science.1249252.
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