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.