HETEROGENEITY IN P53 MUTATIONS IN MOUSE MAMMARY-TUMOR SUBPOPULATIONS WITH DIFFERENT METASTATIC POTENTIAL FROM THE ORTHOTOPIC SITE

We have found that p53 expression is altered with progression to the m etastatic phenotype fo a series of neoplastic subpopulations of a sing le mouse mammary tumor. Single strand conformation polymorphism (SSCP) analysis of p53 transcripts indicate that the expressed p53 genes in each of the subpopulations contain one or more differences from wild t ype p53. Although the mutations in the coding sequence of p53 are diff erent in each of the sublines, suggesting that independent mutational events have occurred, the mutations are clustered in exons 2-4 and in exon 6. In the metastatic subpopulations, there is either a complete l oss of p53 transcriptional activity ol accumulation of transcripts wit h an additional alteration in exons 4-5.