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 |
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Authors: | Nathrath Michaela H Kuosaite Virginija Rosemann Michael Kremer Marcus Poremba Christopher Wakana Shigeharu Yanagi Masayuki Nathrath Walter B J Höfler Heinz Imai Kenji Atkinson Michael J |
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Affiliation: | Institute of Pathology, GSF-National Research Center for Environment and Health, 85764 Neuherberg, Germany. nathrath@gsf.de |
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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/cxCBA/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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