Association of tumorigenic and nontumorigenic (immunogenic) variants in a mouse T-cell lymphoma with two distinct p53 mutations.
An in vitro model system for xenogenization has been developed in which an immunogenic, nonmalignant phenotype was selected from a highly malignant T-cell line (S49). We showed by single-strand conformation polymorphism and DNA sequence analysis that specific point mutations in the p53 tumor suppressor gene correlated with a change from a tumorigenic to a nontumorigenic (immunogenic) phenotype. Specifically, we found that the highly malignant S49 cell line T-60 contains an Arg-->Gln substitution at residue 246 in exon 7 of p53. In contrast, nontumorigenic (immunogenic) variants (T-25-Adh and Rev-1) exhibited a Gly-->Ser substitution at residue 242 of p53. In two subsequent tumorigenic revertants derived from Rev-1, we again found the Arg-->Gln substitution at residue 246 that was found initially in the T-60 cells. Thus, mutation at residue 246 of p53 was associated with a highly malignant phenotype, whereas a novel mutation at residue 242 of p53 appeared to be associated with a nonmalignant phenotype and may have actually protected the host through immunization. We conclude that mutation of residue 242 may represent a new class of permissive (nonmalignant) mutations in the mouse that are analogous to the Li-Fraumeni mutation in humans.
Bergel
M
M
Department of Cell and Animal Biology, Hebrew University of Jerusalem, Israel.
Bhatia
K
K
Siwarski
D
D
Gutierrez
M
M
Hochman
J
J
Huppi
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015342:DNA Probes; D005091:Exons / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D012333:RNA, Messenger