Putative tumor-suppressor gene regions responsible for radiation lymphomagenesis in F1 mice with different p53 status.
Regions of allelic loss on chromosomes in many tumors of human and some experimental animals are generally considered to harbor tumor-suppressor genes involved in tumorigenesis. Allelotype analyses have greatly improved our understanding of the molecular mechanism of radiation lymphomagenesis. Previously, we and others found frequent loss of heterozygosity (LOH) on chromosomes 4, 11, 12, 16 and 19 in radiation-induced lymphomas from several F1 hybrid mice. To examine possible contributions of individual tumor-suppressor genes to tumorigenesis in p53 heterozygous deficiency, we investigated the genome-wide distribution and status of LOH in radiation-induced lymphomas from F1 mice with different p53 status. In this study, we found frequent LOH (more than 20%) on chromosomes 4 and 12 and on chromosomes 11, 12, 16 and 19 in radiation-induced lymphomas from (STS/A X MSM/Ms)F1 mice and (STS/A X MSM/Ms)F1-p53KO/+ mice, respectively. Low incidences of LOH (10-20%) were also observed on chromosomes 11 in mice with wild-type p53, and chromosomes 1, 2, 9, 17 and X in p53 heterozygous-deficient mice. The frequency of LOH on chromosomes 9 and 11 increased in the (STS/A X MSM/Ms)F1-p53KO/+ mice. Preferential losses of the STS-derived allele on chromosome 9 and wild-type p53 allele on chromosome 11 were also found in the p53 heterozygous-deficient mice. Thus, the putative tumor-suppressor gene regions responsible for lymphomaganesis might considerably differ due to the p53 status.
Hong
Doo-Pyo
DP
Research Institute for Advanced Science and Technology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Sakai, Osaka, Japan.
Mori
Nobuko
N
Umesako
Seiichi
S
Song
Chang-Woo
CW
Park
Yeong-Gwan
YG
Aizawa
Shiro
S
Okumoto
Masaaki
M
D000818:Animals; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006579:Heterozygote; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency
D016159:Tumor Suppressor Protein p53