ALLELOTYPE ANALYSIS OF 2',3'-DIDEOXYCYTIDINE-INDUCED AND 1,3-BUTADIENE-INDUCED LYMPHOMAS IN B6C3F1 MICE

To identify potential tumor suppressor genes involved in lymphoma deve lopment, we generated allelotypes of 16 2',3'-dideoxycytidine (ddC) an d 31 1,3-butadiene (BD)-induced lymphomas from C57BL/6 x C3H/He F1 (he reafter called B6C3F1) mice. Two or more anonymous simple sequence len gth polymorphisms per autosome were examined for loss of heterozygosit y (LOH), Allelic losses throughout the genome were generally infrequen t, except for markers on chromosome 2, 4, 11 and 12, The highest frequ ency of allelic losses was observed on chromosome 12, with 38 and 39% in ddC and ED-induced lymphomas, respectively. The most prevalent LOH was localized to the distal region hounded by markers D12Mit263 and D1 2Nds2. No known tumor suppressor genes have been mapped to this region , and no obvious candidates could be identified, suggesting the presen ce of novel suppressor gene(s), LOH on chromosome 2 was observed in 31 % of ddC-induced lymphomas but in only 3% (1/31) of ED-induced lymphom as, suggesting a ddC-specific genetic effect, Detailed analysis Locali zed a potential tumor suppressor gene residing on the distal region of chromosome 2, between markers D2Mit147 and D2Mit148. Twenty-five % of ddC-induced and 23% of BD-induced lymphomas showed LON on chromosome 4, and two discrete regions were identified, One of the regions includ es the IFN gene cluster and is syntenic to human chromosome 9p21-22, C andidate tumor suppressor genes, Mts1 (multiple tumor suppressor 1) an d Mts2 have been mapped to this region, The second region is located o n the distal Dart of chromosome 4, which is homologous to human chromo some 1p35-36, a region that is frequently deleted in various types of human tumors. Finally, 19% of ddC-induced and 29% of BD-induced lympho mas revealed LOH on chromosome 11 at the Acrb locus, which lies within 1 cM of p53, suggesting that the p53 tumor suppressor gene also plays a role in lymphomagenesis. These results suggest that multiple potent ial suppressor loci contribute to lymphoma development in B6C3F1 mice.