The impact of p53 loss on murine plasmacytoma development.
Mouse plasmacytomas (PCTs) are characterized by c-myc-activating translocations that juxtapose c-myc on chromosome 15 onto one of the immunoglobulin loci (IgH on chromosome 12, IgK on chromosome 6, or IgA on chromosome 16). To assess the impact of p53 loss on PCT genesis, we induced PCTs in p53-deficient BALB/cRb6.15 mouse strains. We show that p53 loss accelerates tumor development and causes a shift in the typical translocation patterns. PCTs that carry variant T(6;15) translocations become as frequent as those with typical T(12;15) translocations (41.66%). In addition, in the absence of p53, the number of translocation-negative PCTs increases from less than 1% to 16.66%. It is noteworthy that neither the shortened latency periods nor the shift in translocation patterns had an impact on the incidence of PCT development. The 42.2% incidence in N3p53-/- mice is similar to the percentages recorded in groups of conventional BALB/cAn mice. The possible mechanisms underlying the accelerated tumorigenesis and the shift in translocation patterns are discussed.
Mai
Sabine
S
Manitoba Institute of Cell Biology, The Genomic Centre for Cancer Research and Diagnosis, Department of Physiology, The University of Manitoba, Winnipeg, Canada. smai@cc.umanitoba.ca
Wiener
Francis
F
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D020223:Chromosome Painting; D016259:Genes, myc; D016158:Genes, p53; D019656:Loss of Heterozygosity; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D010954:Plasmacytoma / Q000139:chemically induced / Q000235:genetics*; D013729:Terpenes / Q000633:toxicity; D014178:Translocation, Genetic
D002273:Carcinogens; D013729:Terpenes; C009042:pristane