Analysis of highly frequent allelic loss region on distal chromosome 12 inmurine radiation-induced lymphomas

Recent genetic studies of tumorigenesis have strongly suggested an existenc e of tumor suppressor gene(s) on murine chromosome 12 and human chromosome 14q32. We previously described that putative tumor suppressor gene(s) might reside between D12Mit53 and D12Mit233. We analyzed three genes, Tell, Yyl and Tnf alpha ip2, which had been mapped around the region, as the candidat es in radiation lymphomagenesis of (BALB/c x MSM/Ms)FI hybrid mice. The loc us order and distances of the three genes and microsatellite loci were esti mated as follows: [centromere] - Tcl1-(greater than or equal to 0.085 cM)-D 12Mit50-(0.085 cM)-D12Mit132-(1.96 cM)-D12Mit122-(0.085 cM)-D12Mit53-(1.37 cM)-[D12Mit233,D12Mit279,Yy1]-(0.085 cM)-D12Mit181-( greater than or equal to 0.17 cM)-Tnf alpha ip2 - [telomere]. Allele losses at Tcl1, Yy1 genes an d D12Mit233 were observed in 94(45%), 143(68%) and 147(70%) of 210 lymphoma s, respectively. In semi-quantitative analysis of Yy1 mRNA levels by RT-PCR , kinetics of the yield of the Yy1-cDNA-specific PCR products showed almost the same profiles among thymic lymphomas with allelic loss at Yy1, lymphom as with both alleles retained and normal thymus. These results suggest that Tcl1, Yy1 and Tnf alpha ip2 genes are not predominantly involved in radiat ion 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 o f allelic loss (71%) was observed at the Y184pR2 locus. The LOH patterns of individual lymphomas suggest that putative tumor suppressor gene(s) lies b etween Y152pR1 and Y184pR2. (C) 2000 Elsevier Science Ireland Ltd. All righ ts reserved.