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.