| Co-Investigator(Kenkyū-buntansha) |
FURUTA Masakazu Research Institute for Advanced Science and Technology, Osaka Prefecture University, Research Associate, 先端科学研究所, 助手 (40181458)
MEGUMI Tsuneo Research Institute for Advanced Science and Technology, Osaka Prefecture University, Assistant Professor, 先端科学研究所, 講師 (70090462)
MORI Nobuko Research Institute for Advanced Science and Technology, Osaka Prefecture University, Research Associate, 先端科学研究所, 助手 (90100221)
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| Research Abstract |
We found frequent loss of heterozygosity (LOH) on chromosomes 4, 12 and 19 in radiation-induced lymphomas from (BALB/cHeA x STS/A)FィイD21ィエD2 hybrid mice by allelotype analysis at polymorphic microsatellite loci. The incidences of LOH were 27% (20 of 74 lymphomas), 57% (42/74 lymphomas) and 50% (37/74 lymphomas) on chromosomes 4 (at D4Mit31), 12 (at D12Mit17) and 19 (at D19Mit11), respectively. These frequent LOH regions are homologous to human chromosomes 9p and 1p, chromosome 14q32.1 and chromosome 10q, respectively. Strain-specific preferential allele loss on only chromosome 4 was observed. However, no bias in the frequency of loss between alleles of maternal and paternal origin was observed, indicating that genomic imprinting may not be predominantly involved in these lymphomas. The results suggest that these three regions might harbor tumor suppressor genes responsible for the lymphomagenesis.
We also found that putative tumor suppressor gene(s) might reside between D12Mit53 and D12Mit233. We analyzed three genes, Tcl1, Yy1 and Tnfaip2, which had been mapped around the region on distal chromosome 12, as the candidates in radiation lymphomagenesis of (BALB/c x MSM/Ms)FィイD21ィエD2 hybrid mice. The results suggest that Tcl1, Ty1, and Tnfaip2 genes are not predominantly involved in radiation lymphomagenesis of mice. In further analysis of the common allelic loss region, we found new loci, Y152pR1 and Y184pR2, from YACs which located in the hot region between D12Mit53 and D12Mit233, and the highest frequency, of allelic loss (71%) was observed at the Y184pR2 locus. The LOH patterns of individual lymphomas suggest that putative tumor suppressor gene(s) lies between Y152pR1 and Y184pR2.
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