Genetic analysis of radiation-induced thymic lymphoma

Mouse thymic lymphomas are one of the classic models of radiation-induced malignancies. However, little genetic study has been performed, although the mouse systems offer a number of useful features for genetic and physical mapping. We have carried out large-scale mapping toward the isolation of the genes involved in lymphoma development. Two different types of genes are chosen as targets for positional cloning. One is the tumor suppressor gene and the other is the susceptibility or resistance-giving gene, which predispose to the lymphoma development. One susceptibility locus was localized near D4Mit12 on chromosome 12 by an association study for backcross and congenic mice, and three loci, probably harboring a tumor suppressor gene, were localized by allelic loss mapping on physical maps that were covered by BAC clones. The maps are invaluable to facilitate the identification of candidate tumor suppressor genes. Also, success in identification of Ikaros as a tumor suppressor gene is described.