Homozygous deletions and point mutations of the Ikaros gene in gamma-ray-induced mouse thymic lymphomas

Our previous genome-wide analysis of allelic loss for thymic lymphomas that were induced by gamma-irradiation in F-1 hybrid mice between BALB/c and MS M strains suggested the centromeric region on chromosome 11 as a site harbo ring a tumor suppressor gene. Interestingly, to this region the mouse Ikaro s gene was mapped which was postulated to participate in oncogenic process from the study of Ikaros knockout mice. Here we show fine allelic loss mapp ing in the vicinity of Ikaros in 191 lymphomas, indicating that the critica l region of allelic loss was centered at the Ikaros locus. PCR analysis rev ealed that nine lymphomas failed to give PCR-amplification for either of tw o exon primer pairs, indicative of homozygous deletion, Six and five mutati ons were detected in the N-terminal zinc finger domain and the activation d omain of Ikaros, respectively, and six of the eleven were frameshift or non sense mutations that resulted in truncation of Ikaros protein. The results strongly suggest a direct role for Ikaros in development of mouse thymic ly mphomas, This provides the experimental basis for further analysis of Ikaro s mutations in human cancer.