Infrequent p53 Mutation in Mouse Tumors with Deregulated myc

An invariant genetic lesion in mouse plasmacytomas is deregulated expression of c- myc as a consequence of chromosomal translocation. However, retroviral and transgenic studies suggest that additional genetic lesions may contribute to the genesis of plasmacytomas. The p53 tumor suppressor gene is a likely contributor to this genetic lesion, since there is a high incidence of p53 mutation in Burkitt's lymphomas and B-ALL (L3), both of which contain translocations involving c- myc analogous to those in plasmacytomas. In addition, p53 has been shown to be a transcriptional modulator of c- myc expression. In a survey of 27 mouse plasmacytomas by single-strand conformation polymorphism, we identified a single mutation (3.7% incidence), suggesting that p53 lesions are not frequent contributors to plasmacytomagenesis. A similar study of macrophage-monocyte tumors generated by a c- myc -containing retrovirus also indicates a lack of p53 involvement in deregulated c- myc expression. These results suggest that the specific maturation stage of transformed B-lymphocytes, independent of c- myc deregulation, may be the critical factor which determines the involvement of mutant p53 .