Abstract
The breakage-fusion-bridge (BFB) mechanism was proposed over seven decades ago and is a source of genomic variability and gene amplification in cancer. Here we formally model and analyze the BFB mechanism, to our knowledge this first time this has been undertaken. We show that BFB can be modeled as successive inverted prefix duplications of a string. Using this model, we show that BFB can achieve a surprisingly broad range of amplification patterns. We find that a sequence of BFB operations can be found that nearly fits most patterns of copy number increases along a chromosome. We conclude that this limits the usefulness of methods like array CGH for detecting BFB and discuss other implications for understanding mechanisms of genomic instability.
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References
Artandi, S.E., DePinho, R.A.: Telomeres and telomerase in cancer. Carcinogenesis 31, 9–18 (2010)
Bignell, G.R., Santarius, T., Pole, J.C., Butler, A.P., Perry, J., Pleasance, E., Greenman, C., Menzies, A., Taylor, S., Edkins, S., Campbell, P., Quail, M., Plumb, B., Matthews, L., McLay, K., Edwards, P.A., Rogers, J., Wooster, R., Futreal, P.A., Stratton, M.R.: Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution. Genome Res. 17, 1296–1303 (2007)
Deza, M.M., Deza, E.: Encyclopedia of Distances. Springer (2009)
Kitada, K., Yamasaki, T.: The complicated copy number alterations in chromosome 7 of a lung cancer cell line is explained by a model based on repeated breakage-fusion-bridge cycles. Cancer Genet. Cytogenet. 185, 11–19 (2008)
McClintock, B.: The Production of Homozygous Deficient Tissues with Mutant Characteristics by Means of the Aberrant Mitotic Behavior of Ring-Shaped Chromosomes. Genetics 23, 315–376 (1938)
McClintock, B.: The Stability of Broken Ends of Chromosomes in Zea Mays. Genetics 26, 234–282 (1941)
Santarius, T., Shipley, J., Brewer, D., Stratton, M.R., Cooper, C.S.: A census of amplified and overexpressed human cancer genes. Nat. Rev. Cancer 10, 59–64 (2010)
Shimizu, N., Shingaki, K., Kaneko-Sasaguri, Y., Hashizume, T., Kanda, T.: When, where and how the bridge breaks: anaphase bridge breakage plays a crucial role in gene amplification and HSR generation. Exp. Cell Res. 302, 233–243 (2005)
Zhao, X., Li, C., Paez, J.G., Chin, K., Janne, P.A., Chen, T.H., Girard, L., Minna, J., Christiani, D., Leo, C., Gray, J.W., Sellers, W.R., Meyerson, M.: An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays. Cancer Res. 64, 3060–3071 (2004)
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Kinsella, M., Bafna, V. (2012). Modeling the Breakage-Fusion-Bridge Mechanism: Combinatorics and Cancer Genomics. In: Chor, B. (eds) Research in Computational Molecular Biology. RECOMB 2012. Lecture Notes in Computer Science(), vol 7262. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-29627-7_13
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DOI: https://doi.org/10.1007/978-3-642-29627-7_13
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-29626-0
Online ISBN: 978-3-642-29627-7
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