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  • Original Paper
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Two novel tumor suppressor gene loci on chromosome 6q and 15q in human osteosarcoma identified through comparative study of allelic imbalances in mouse and man

Oncogene volume 21, pages 5975–5980 (2002)Cite this article

Abstract

We have performed a comparative study of allelic imbalances in human and murine osteosarcomas to identify genetic changes critical for osteosarcomagenesis. Two adjacent but discrete loci on mouse chromosome 9 were found to show high levels of allelic imbalance in radiation-induced osteosarcomas arising in (BALB/c×CBA/CA) F1 hybrid mice. The syntenic human chromosomal regions were investigated in 42 sporadic human osteosarcomas. For the distal locus (OSS1) on mouse chromosome 9 the syntenic human locus was identified on chromosome 6q14 and showed allelic imbalance in 77% of the cases. Comparison between the human and mouse syntenic regions narrowed the locus down to a 4 Mbp fragment flanked by the marker genes ME1 and SCL35A1. For the proximal locus (OSS2) on mouse chromosome 9, a candidate human locus was mapped to chromosome 15q21 in a region showing allelic imbalance in 58% of human osteosarcomas. We have used a combination of synteny and microsatellite mapping to identify two potential osteosarcoma suppressor gene loci. This strategy represents a powerful tool for the identification of new genes important for the formation of human tumors.

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Acknowledgements

We thank Utz Linzner for oligonucleotide preparation and Wibke Wistrich for excellent technical assistance. Parts of this project were funded by grant F14P-CT95-0008 from the Radiation protection program of the European Union (M Rosemann) and from the Land Bayern (M Nathrath: HSP III) and the clinical research fund ‘KKF’ of the Technical University Munich (M Nathrath).

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Authors and Affiliations

  1. Institute of Pathology, GSF-National Research Center for Environment and Health, Neuherberg, 85764, Germany

    Michaela H Nathrath, Virginija Kuosaite, Michael Rosemann, Masayuki Yanagi, Heinz Höfler & Michael J Atkinson

  2. Department of Pediatrics, Technical University of Munich, Munich, 80804, Germany

    Michaela H Nathrath

  3. Institute of Pathology, Technical University of Munich, Munich, 81675, Germany

    Marcus Kremer & Heinz Höfler

  4. Institute of Pathology, Heinrich-Heine-University, Duesseldorf, 40225, Germany

    Christopher Poremba

  5. Mouse Functional Genomics Research Group, RIKEN Genomics Sciences Center, Yokohama, 224-0804, Japan

    Shigeharu Wakana

  6. Institute of Pathology, Municipal Hospital München-Harlaching, Munich, 81545, Germany

    Walter BJ Nathrath

  7. Institute of Mammalian Genetics, GSF-National Research Center for Environment and Health, Neuherberg, 85764, Germany

    Kenji Imai

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  1. Michaela H Nathrath
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  2. Virginija Kuosaite
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Correspondence to Michaela H Nathrath.

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Nathrath, M., Kuosaite, V., Rosemann, M. et al. Two novel tumor suppressor gene loci on chromosome 6q and 15q in human osteosarcoma identified through comparative study of allelic imbalances in mouse and man. Oncogene 21, 5975–5980 (2002). https://doi.org/10.1038/sj.onc.1205764

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  • DOI: https://doi.org/10.1038/sj.onc.1205764

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