Abstract
Radiation-induced mouse thymic lymphoma is a useful model for studying not only the mechanism of radiation carcinogenesis but also genetic susceptibility to tumor development. Using array-comparative genomic hybridization, we analyzed genome-wide DNA copy number changes in radiation-induced thymic lymphomas developed in susceptible C57BL/6, resistant C3H and the relatively susceptible hybrids C3B6F1 and B6C3F1. Besides aberrations at known relevant genetic loci including Ikaros and Bcl11b and trisomy of chromosome 15, we newly identified strain-dependent genomic imbalances on chromosomes 5, 10 and 16, and strain-independent trisomy of chromosome 14 as frequent aberrations. In addition, biallelic rearrangements at Tcrb were more frequently detected in tumors of C57BL/6 than C3H, suggesting aberrant V(D)J recombination and a possible link with tumor susceptibility. The frequency and spectrum of these copy-number changes in lymphomas of C3B6F1 and B6C3F1 were similar to that of C57BL/6. Furthermore, in combination with loss of heterozygosity analysis of F1 tumors, it was suggested that allelic losses at Ikaros and Bcl11b were primarily caused by multilocus deletion, whereas those at Cdkn2 and Pten loci were mainly due to uniparental disomy. These findings provide important clues to both the mechanisms for accumulation of aberrations during radiation-induced lymphomagenesis and different susceptibility among mouse strains. This study was supported by a grant from Aomori Prefecture, Japan.
