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  • Oncogenomics
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Genomic profiling of bone and soft tissue tumors with supernumerary ring chromosomes using tiling resolution bacterial artificial chromosome microarrays

Oncogene volume 25, pages 7106–7116 (2006)Cite this article

Abstract

Ring chromosomes and/or giant marker chromosomes have been observed in a variety of human tumor types, but they are particularly common in a subgroup of mesenchymal tumors of low-grade or borderline malignancy. These rings and markers have been shown to contain amplified material predominantly from 12q13–15, but also sequences from other chromosomes. Such amplified sequences were mapped in detail by genome-wide array comparative genomic hybridization in ring-containing tumor samples from soft tissue (n=15) and bone (n=6), using tiling resolution microarrays, encompassing 32 433 bacterial artificial chromosome clones. The DNA copy number profiles revealed multiple amplification targets, in many cases highly discontinuous, leading to delineation of large numbers of very small amplicons. A total number of 356 (median size: 0.64 Mb) amplicons were seen in the soft tissue tumors and 90 (median size: 1.19 Mb) in the bone tumors. Notably, more than 40% of all amplicons in both soft tissue and bone tumors were mapped to chromosome 12, and at least one of the previously reported recurrent amplifications in 12q13.3–14.1 and 12q15.1, including SAS and CDK4, and MDM2, respectively, were present in 85% of the soft tissue tumors and in all of the bone tumors. Although chromosome 12 was the only chromosome displaying recurrent amplification in the bone tumors, the soft tissue tumors frequently showed recurrent amplicons mapping to other chromosomes, that is, 1p32, 1q23–24, 3p11–12, 6q24–25 and 20q11–12. Of particular interest, amplicons containing genes involved in the c-jun NH2-terminal kinase/mitogen-activated protein kinase pathway, that is, JUN in 1p32 and MAP3K7IP2 (TAB2) in 6q24–25, were found to be independently amplified in eight of 11 cases with 12q amplification, providing strong support for the notion that aberrant expression of this pathway is an important step in the dedifferentiation of liposarcomas.

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References

  • Autio R, Hautaniemi S, Kauraniemi P, Yli-Harja O, Astola J, Wolf M et al. (2003). Bioinformatics 19: 1714–1715.

  • Berner JM, Forus A, Elkahloun A, Meltzer PS, Fodstad O, Myklebost O . (1996). Genes Chromosomes Cancer 17: 254–259.

  • Chibon F, Mariani O, Derre J, Mairal A, Coindre JM, Guillou L et al. (2004). Genes Chromosomes Cancer 40: 32–37.

  • Chibon F, Mariani O, Derre J, Malinge S, Coindre JM, Guillou L et al. (2002). Cancer Genet Cytogenet 139: 24–29.

  • Coindre JM, Hostein I, Maire G, Derre J, Guillou L, Leroux A et al. (2004). J Pathol 203: 822–830.

  • Coindre JM, Mariani O, Chibon F, Mairal A, De Saint Aubain Somerhausen N, Favre-Guillevin E et al. (2003). Mod Pathol 16: 256–262.

  • Dahlén A, Debiec-Rychter M, Pedeutour F, Domanski HA, Höglund M, Bauer HC et al. (2003). Int J Cancer 103: 616–623.

  • Dal Cin P, Kools P, Sciot R, De Wever I, Van Damme B, Van de Ven W et al. (1993). Cancer Genet Cytogenet 68: 85–90.

  • Forus A, Berner JM, Meza-Zepeda LA, Saeter G, Mischke D, Fodstad O et al. (1998). Br J Cancer 78: 495–503.

  • Forus A, Weghuis DO, Smeets D, Fodstad O, Myklebost O, Geurts van Kessel A . (1995a). Genes Chromosomes Cancer 14: 8–14.

  • Forus A, Weghuis DO, Smeets D, Fodstad O, Myklebost O, Geurts van Kessel A . (1995b). Genes Chromosomes Cancer 14: 15–21.

  • Gamberi G, Ragazzini P, Benassi MS, Ferrari C, Sollazzo MR, Molendini L et al. (2000). Clin Orthop Relat Res 377: 195–204.

  • Gisselsson D, Pålsson E, Höglund M, Domanski H, Mertens F, Pandis N et al. (2002). Genes Chromosomes Cancer 33: 133–140.

  • Heidenblad M, Lindgren D, Veltman JA, Jonson T, Mahlamäki EH, Gorunova L et al. (2005). Oncogene 24: 1794–1801.

  • Jönsson G, Bendahl PO, Sandberg T, Kurbasic A, Staaf J, Sunde L et al. (2005). J Natl Cancer Inst 97: 1377–1382.

  • Kanoe H, Nakayama T, Hosaka T, Murakami H, Yamamoto H, Nakashima Y et al. (1999). Oncogene 18: 721–729.

  • Kresse SH, Berner JM, Meza-Zepeda LA, Gregory SG, Kuo WL, Gray JW et al. (2005). Mol Cancer 4: 39.

  • Mairal A, Terrier P, Chibon F, Sastre X, Lecesne A, Aurias A . (1999). Cancer Genet Cytogenet 111: 134–138.

  • Mansoor A, Fidda N, Himoe E, Payne M, Lawce H, Magenis RE . (2004). Cancer Genet Cytogenet 152: 61–65.

  • Meltzer PS, Jankowski SA, Dal Cin P, Sandberg AA, Paz IB, Coccia MA . (1991). Cell Growth Differ 2: 495–501.

  • Mertens F, Fletcher CDM, Dal Cin P, De Wever I, Mandahl N, Mitelman F et al. (1998). Genes Chromosomes Cancer 22: 16–25.

  • Mertens F, Panagopoulos I, Jonson T, Gisselsson D, Isaksson M, Domanski HA et al. (2004). Cytogenet Genome Res 106: 33–38.

  • Meza-Zepeda LA, Berner JM, Henriksen J, South AP, Pedeutour F, Dahlberg AB et al. (2001). Genes Chromosomes Cancer 31: 264–273.

  • Meza-Zepeda LA, Forus A, Lygren B, Dahlberg AB, Godager LH, South AP et al. (2002). Oncogene 21: 2261–2269.

  • Micci F, Teixeira MR, Bjerkehagen B, Heim S . (2002). Cytogenet Genome Res 97: 13–19.

  • Mitelman F, Johansson B, Mertens F . (2005). Mitelman database of chromosome aberrations in cancer Available at:http://cgap.nci.nih.gov/Chromosomes/Mitelman.

  • Nilbert M, Rydholm A, Willén H, Mitelman F, Mandahl N . (1994). Genes Chromosomes Cancer 9: 261–265.

  • Nilsson M, Meza-Zepeda LA, Mertens F, Forus A, Myklebost O, Mandahl N . (2004). Int J Cancer 109: 363–369.

  • Örndal C, Mandahl N, Rydholm A, Willén H, Brosjö O, Heim S et al. (1992). Cancer Genet Cytogenet 60: 170–175.

  • Pedeutour F, Forus A, Coindre JM, Berner JM, Nicolo G, Michiels JF et al. (1999). Genes Chromosomes Cancer 24: 30–41.

  • Pedeutour F, Suijkerbuijk RF, Forus A, Van Gaal J, Van de Klundert W, Coindre JM et al. (1994). Genes Chromosomes Cancer 10: 85–94.

  • Platzer P, Upender MB, Wilson K, Willis J, Lutterbaugh J, Nosrati A et al. (2002). Cancer Res 62: 1134–1138.

  • Saal LH, Troein C, Vallon-Christersson J, Gruvberger S, Borg Å, Peterson C . (2002). Genome Biol 3: SOFTWARE0003.

  • Sabah M, Cummins R, Leader M, Kay E . (2005). Virchows Arch 447: 842–848.

  • Simons A, Schepens M, Jeuken J, Sprenger S, van de Zande G, Bjerkehagen B et al. (2000). Cancer Genet Cytogenet 118: 89–98.

  • Sirvent N, Maire G, Pedeutour F . (2003). Genes Chromosomes Cancer 37: 1–19.

  • Smith DI, Zhu Y, McAvoy S, Kuhn R . (2005). Cancer Lett 232: 48–57.

  • Szymanska J, Mandahl N, Mertens F, Tarkkanen M, Karaharju E, Knuutila S . (1996). Genes Chromosomes Cancer 16: 31–34.

  • Szymanska J, Virolainen M, Tarkkanen M, Wiklund T, Asko-Seljavaara S, Tukiainen E et al. (1997). Cancer Genet Cytogenet 99: 14–18.

  • Yang YH, Dudoit S, Luu P, Lin DM, Peng V, Ngai J et al. (2002). Nucleic Acids Res 30: e15.

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Acknowledgements

This work was supported by the Swedish Cancer Society, the Swedish Children's Cancer Foundation, the Crafoord Foundation, the Gunnar Nilsson's Cancer Foundation, the Knut and Alice Wallenberg foundation via the Swegene program, the Ingabritt and Arne Lundberg Foundation, and the Royal Physiographic Society in Lund.

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Authors and Affiliations

  1. Department of Clinical Genetics, Lund University Hospital, Lund, Sweden

    M Heidenblad, K H Hallor, M Höglund, F Mertens & N Mandahl

  2. Department of Oncology, Lund University Hospital, Lund, Sweden

    J Staaf, G Jönsson & Å Borg

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  1. M Heidenblad
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  2. K H Hallor
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  3. J Staaf
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Correspondence to M Heidenblad.

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

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Heidenblad, M., Hallor, K., Staaf, J. et al. Genomic profiling of bone and soft tissue tumors with supernumerary ring chromosomes using tiling resolution bacterial artificial chromosome microarrays. Oncogene 25, 7106–7116 (2006). https://doi.org/10.1038/sj.onc.1209693

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