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  • Oncogenomics
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DNA copy number amplification profiling of human neoplasms

Oncogene volume 25, pages 7324–7332 (2006)Cite this article

Abstract

DNA copy number amplifications activate oncogenes and are hallmarks of nearly all advanced tumors. Amplified genes represent attractive targets for therapy, diagnostics and prognostics. To investigate DNA amplifications in different neoplasms, we performed a bibliomics survey using 838 published chromosomal comparative genomic hybridization studies and collected amplification data at chromosome band resolution from more than 4500 cases. Amplification profiles were determined for 73 distinct neoplasms. Neoplasms were clustered according to the amplification profiles, and frequently amplified chromosomal loci (amplification hot spots) were identified using computational modeling. To investigate the site specificity and mechanisms of gene amplifications, colocalization of amplification hot spots, cancer genes, fragile sites, virus integration sites and gene size cohorts were tested in a statistical framework. Amplification-based clustering demonstrated that cancers with similar etiology, cell-of-origin or topographical location have a tendency to obtain convergent amplification profiles. The identified amplification hot spots were colocalized with the known fragile sites, cancer genes and virus integration sites, but global statistical significance could not be ascertained. Large genes were significantly overrepresented on the fragile sites and the reported amplification hot spots. These findings indicate that amplifications are selected in the cancer tissue environment according to the qualitative traits and localization of cancer genes.

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References

  • Albertson DG, Collins C, McCormick F, Gray JW . (2003). Nat Genet 34: 369–376.

  • Atiye J, Wolf M, Kaur S, Monni O, Bohling T, Kivioja A et al. (2005). Genes Chromosomes Cancer 42: 158–163.

  • Bernasconi P, Calatroni S, Giardini I, Inzoli A, Castagnola C, Cavigliano PM et al. (2005). Cancer Genet Cytogenet 162: 146–150.

  • Birney E, Andrews TD, Bevan P, Caccamo M, Chen Y, Clarke L et al. (2004). Genome Res 14: 925–928.

  • Buttel I, Fechter A, Schwab M . (2004). Ann NY Acad Sci 1028: 14–27.

  • El-Rifai W, Sarlomo-Rikala M, Knuutila S, Miettinen M . (1998). Am J Pathol 153: 985–990.

  • Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R et al. (2004). Nat Rev Cancer 4: 177–183.

  • Glover TW, Berger C, Coyle J, Echo B . (1984). Hum Genet 67: 136–142.

  • Goker E, Waltham M, Kheradpour A, Trippett T, Mazumdar M, Elisseyeff Y et al. (1995). Blood 86: 677–684.

  • Good P . (2000). Permutation Tests: A Practical Guide to Resampling Methods for Testing Hypotheses. Springer-Verlag: Berlin.

    Book  Google Scholar 

  • Graux C, Cools J, Melotte C, Quentmeier H, Ferrando A, Levine R et al. (2004). Nat Genet 36: 1084–1089.

  • Guan XY, Meltzer PS, Dalton WS, Trent JM . (1994). Nat Genet 8: 155–161.

  • Hahn PJ . (1993). Bioessays 15: 477–484.

  • Hellman A, Zlotorynski E, Scherer SW, Cheung J, Vincent JB, Smith DI et al. (2002). Cancer Cell 1: 89–97.

  • Himberg J, Hyvärinen A . (2001). In: Lee T-W, Jung T-P, Makeig S, Sejnowski TJ (eds). Third International Workshop on Independent Component Analysis and Blind Signal Separation (ICA2001). Institute for Neural Computation, University of California San Diego: San Diego, CA, USA, pp 552–556.

    Google Scholar 

  • Himberg J, Hyvärinen A, Esposito F . (2004). Neuroimage 22: 1214–1222.

  • Hyman E, Kauraniemi P, Hautaniemi S, Wolf M, Mousses S, Rozenblum E et al. (2002). Cancer Res 62: 6240–6245.

  • Hyvärinen A, Oja E, Karhunen J . (2001). Independent Component Analysis. John Wiley & Sons: New York.

    Book  Google Scholar 

  • ISCN (1995). An International System for Human Cytogenetic Nomenclature. S Karger: Basel.

  • Johnston RN, Beverley SM, Schimke RT . (1983). Proc Natl Acad Sci USA 80: 3711–3715.

  • Knuutila S, Autio K, Aalto Y . (2000). Am J Pathol 157: 689.

  • Lengauer C, Kinzler KW, Vogelstein B . (1998). Nature 396: 643–649.

  • Livingstone LR, White A, Sprouse J, Livanos E, Jacks T, Tlsty TD . (1992). Cell 70: 923–935.

  • Looijenga LH, Oosterhuis JW . (1999). Rev Reprod 4: 90–100.

  • Maurer BJ, Lai E, Hamkalo BA, Hood L, Attardi G . (1987). Nature 327: 434–437.

  • Monni O, Franssila K, Joensuu H, Knuutila S . (1999). Leukamia Lymphoma 34: 45–52.

  • Myllykangas S, Knuutila S . (2006). Cancer Lett 232: 79–89.

  • Ozaki T, Schaefer KL, Wai D, Buerger H, Flege S, Lindner N et al. (2002). Int J Cancer 102: 355–365.

  • Pollack JR, Perou CM, Alizadeh AA, Eisen MB, Pergamenschikov A, Williams CF et al. (1999). Nat Genet 23: 41–46.

  • Pollack JR, Sorlie T, Perou CM, Rees CA, Jeffrey SS, Lonning PE et al. (2002). Proc Natl Acad Sci USA 99: 12963–12968.

  • Rieker RJ, Joos S, Bartsch C, Willeke F, Schwarzbach M, Otano-Joos M et al. (2002). Int J Cancer 99: 68–73.

  • Roumier C, Fenaux P, Lafage M, Imbert M, Eclache V, Preudhomme C . (2003). Leukemia 17: 9–16.

  • Schwab M . (1998). Bioessays 20: 473–479.

  • Schwab M . (2004). Cancer Lett 204: 179–187.

  • Sell S . (2004). Crit Rev Oncol Hematol 51: 1–28.

  • Shannon KM . (2002). Cancer Cell 2: 99–102.

  • Torchia EC, Jaishankar S, Baker SJ . (2003). Cancer Res 63: 3464–3468.

  • Wahl GM, Padgett RA, Stark GR . (1979). J Biol Chem 254: 8679–8689.

  • Weng WH, Ahlen J, Lui WO, Brosjo O, Pang ST, Von Rosen A et al. (2003). Br J Cancer 89: 720–726.

  • Yin Y, Tainsky MA, Bischoff FZ, Strong LC, Wahl GM . (1992). Cell 70: 937–948.

  • Zatkova A, Ullmann R, Rouillard JM, Lamb BJ, Kuick R, Hanash SM et al. (2004). Genes Chromosomes Cancer 39: 263–276.

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Acknowledgements

This research was supported by grants from the Finnish Academy (SYSBIO Research Program), the Helsinki University Central Hospital Research Funds and the Sigrid Jusélius Foundation. The University of Helsinki, the Helsinki University of Technology and the HUSLAB provided the research facilities and the equipment used in this study.

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Authors and Affiliations

  1. Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

    S Myllykangas, T Böhling, B Nagy & S Knuutila

  2. Laboratory of Computer and Information Science, Helsinki University of Technology, Espoo, Finland

    J Himberg & J Hollmén

  3. 1st Department of Obstetrics and Gynecology, Scmmclwcis University, Budapest, Hungary

    B Nagy

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  1. S Myllykangas
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  2. J Himberg
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  3. T Böhling
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  4. B Nagy
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Correspondence to S Myllykangas.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc).

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Myllykangas, S., Himberg, J., Böhling, T. et al. DNA copy number amplification profiling of human neoplasms. Oncogene 25, 7324–7332 (2006). https://doi.org/10.1038/sj.onc.1209717

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