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.
Gutierrez
M I
MI
Pediatrics Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Bhatia
K
K
Siwarski
D
D
Wolff
L
L
Magrath
I T
IT
Mushinski
J F
JF
Huppi
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D016158:Genes, p53; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D010954:Plasmacytoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense