Amplification and rearrangement of c-myc in radiation-induced murine osteosarcomas.
Fifty-one radiation-induced murine osteosarcomas were investigated for alterations in c-myc gene structure and c-myc expression. Amplification of c-myc was found in 30% of BALB/c tumors and 13% of NMRI tumors. A region of common proviral integration, Mlvi-1, localized on the same region on chromosome 15, was amplified concomitantly. Multiple copies of both loci were localized on double minutes. Three of the tumors with c-myc amplification also showed rearrangements of the c-myc gene region. One of these rearrangements included the 5' and 3'-flanking sequences and the noncoding part of the third exon. Repetitive sequences were found in the 5' region of the c-myc gene, and the 3' flanking region was substituted by sequences normally present in a more distant part of chromosome 15. Increased levels of c-myc transcripts of apparently normal size were found in tumors carrying amplified c-myc sequences. Abnormally high expression of c-myc in some tumors was correlated with an early stage of osteogenic differentiation, suggesting the involvement of the c-myc gene in the control of the osteogenic differentiation of transformed cells.
Sturm
S A
SA
GSF-Abteilung für Molekulare Zellpathologie, Neuherberg, Federal Republic of Germany.
Strauss
P G
PG
Adolph
S
S
Hameister
H
H
Erfle
V
V
D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D005784:Gene Amplification / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D015698:Genomic Library; D007621:Karyotyping; D051379:Mice; D008807:Mice, Inbred BALB C; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics*; D009857:Oncogenes; D053495:Osteopontin; D012516:Osteosarcoma / Q000209:etiology / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016760:Proto-Oncogene Proteins c-fos; D017231:Proto-Oncogene Proteins c-mos; D012334:RNA, Neoplasm / Q000032:analysis*; D012795:Sialoglycoproteins / Q000032:analysis
D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012334:RNA, Neoplasm; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D017231:Proto-Oncogene Proteins c-mos