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.
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.
Institute of Pathology, GSF-National Research Center for Environment and Health, 85764 Neuherberg, Germany. nathrath@gsf.de
Michaela H
MH
Nathrath
Virginija
V
Kuosaite
Michael
M
Rosemann
Marcus
M
Kremer
Christopher
C
Poremba
Shigeharu
S
Wakana
Masayuki
M
Yanagi
Walter B J
WB
Nathrath
Heinz
H
Höfler
Kenji
K
Imai
Michael J
MJ
Atkinson
D000483:Alleles; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001859:Bone Neoplasms / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15; D002896:Chromosomes, Human, Pair 6; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D018895:Microsatellite Repeats; D012516:Osteosarcoma / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C489532:Tcf12 protein, mouse; C073366:TCF12 protein, human