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Association of tumorigenic and nontumorigenic (immunogenic) variants in a mouse t‐cell lymphoma with two distinct p53 mutations
Author(s) -
Bergel Michael,
Hochman Jacob,
Siwarski David,
Huppi Konrad,
Bhatia Kishor,
Gutierrez Marina
Publication year - 1993
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940080404
Subject(s) - biology , phenotype , exon , point mutation , mutation , gene , genetics , microbiology and biotechnology , cancer research , cell culture , lymphoma , immunology
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. © 1993 Wiley‐Liss, Inc.