Evidence of a possible epigenetic inactivation mechanism operating on a region of mouse chromosome 19 in gamma-radiation-induced thymic lymphomas

Loss of heterozygosity (LOH) analysis, performed in 68 gamma -radiation-ind uced primary thymic lymphomas of F1 hybrid mice, provided evidence of signi ficant LOH on chromosome 19 in a region defined by the D19Mit106 (22 cM) an d D19Mit100 (27 cM) markers (Thymic Lymphoma Suppressor Region 8, TLSR8), C d95 and Pten, two genes mapped at this region, were inactivated in a vast m ajority of these tumors (85.3% for Cd95 and 61.8% for Pten), Moreover, alte red expression of Cd95 and Pten occurred concomitantly in 34 of 68 (50%) th ymic lymphomas suggesting a coordinated mechanism of inactivation of these genes. Surprisingly, we also found that Jak2, a proto-oncogene located betw een Cd95 and Pten, was simultaneously inactivated in a significant fraction of the tumors analysed (24 of 34, 70.6%). Taken together these findings an d the lack of mutations in the coding sequences of the mentioned genes clea rly suggest a possible regional epigenetic inactivation mechanism on mouse chromosome 19 operating during the development of these tumors.