Expression of cellular oncogenes: unrearranged c-myc gene but altered promoter usage in radiation-induced thymoma.

Expression of eleven oncogenes was analyzed in thymomas induced by X-rays in the BALB/c strain of mice. H-, K-, N-ras, c-myc, c-myb, and c-abl genes were consistently expressed in thymomas, as well as in normal, age-matched thymus. Only c-myc transcription appeared to be altered in thymomas: a 1.5-3-fold elevated expression of c-myc was found in 42% of the thymomas tested. An altered ratio of two normal promoters, P1 and P2, of the c-myc gene has also been observed in 6 samples out of 15 tested. In one sample, expression from only the P2 promoter was found. A change in DNA sequence to the 5' side of this promoter was detected in an RNAase cleavage assay; this could have disrupted transcription from the P1 promoter. No other structural alteration has been detected within approximately 1800 bases upstream or 700 bases downstream from the 1st exon including exon 1 of the c-myc gene. With the exception of the one sample described, the results of RNAase cleavage assays, as well as Southern blotting of the c-myc gene, show that the structural alteration of this region of c-myc is not generally associated with radiation-induced thymomas in this strain of mice.