We have been studying the multistep process of transformation in B-cell lineage tumors that arise in transgenic mice which overexpress the myc oncogene under transcriptional regulation of mutant or wild type immunoglobulin heavy chain enhancer constructs. In order to identify genes that collaborate in transformation with the inappropriately expressed myc gene, we use a PCR-based assay capable of quantifying expression of 20 candidate oncogenes. Our most interesting observations involve the p53 tumor suppressor gene. In 30% of the B-lineage tumors there is very little if any p53 mRNA. Among those tumors that do express abundant p53 RNA, an additional 20% have point mutations detectable in SSCP assays that examined only two of the eleven p53 exons. An expanded set of SSCP assays covering the remaining p53 exons is currently underway. Thus, a minimum of 50% of the B-lineage tumors have down regulated p53 expression or are expressing mutated versions of the gene. These results strongly suggest that myc gene dysregulation often leads to p53 gene dysregulation and that these two events are common events in the process of B cell tumorigenesis.
