Analysis of changes in DNA copy number in radiation-induced thymic lymphomas of susceptible C57BL/6, resistant C3H and hybrid F1 Mice.
Radiation-induced thymic lymphoma in mice is a useful model for studying both the mechanism of radiation carcinogenesis and genetic susceptibility to tumor development. Using array-comparative genomic hybridization, we analyzed genome-wide changes in DNA copy numbers in radiation-induced thymic lymphomas that had developed in susceptible C57BL/6 and resistant C3H mice and their hybrids, C3B6F1 and B6C3F1 mice. Besides aberrations at known relevant genetic loci including Ikaros and Bcl11b and trisomy of chromosome 15, we identified strain-associated genomic imbalances on chromosomes 5, 10 and 16 and strain-unassociated trisomy of chromosome 14 as frequent aberrations. In addition, biallelic rearrangements at Tcrb were detected more frequently in tumors from C57BL/6 mice than in those from C3H mice, suggesting aberrant V(D)J recombination and a possible link with tumor susceptibility. The frequency and spectrum of these copy-number changes in lymphomas from C3B6F1 and B6C3F1 mice were similar to those in C57BL/6 mice. Furthermore, the loss of heterozygosity analyses of tumors in F(1) mice indicated that allelic losses at Ikaros and Bcl11b were caused primarily by multilocus deletions, whereas those at the Cdkn2a/Cdkn2b and Pten loci were due mainly to uniparental disomy. These findings provide important clues to both the mechanisms for accumulation of aberrations during radiation-induced lymphomagenesis and the different susceptibilities of C57BL/6 and C3H mice.
Takabatake
Takashi
T
Department of Radiobiology, Institute for Environmental Sciences, Hacchazawa 2-121, Takahoko, Rokkasho, Aomori 039-3213, Japan. batake@nirs.go.jp
Kakinuma
Shizuko
S
Hirouchi
Tokuhisa
T
Nakamura
Masako M
MM
Fujikawa
Katsuyoshi
K
Nishimura
Mayumi
M
Oghiso
Yoichi
Y
Shimada
Yoshiya
Y
Tanaka
Kimio
K
D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D018628:Gene Dosage; D016130:Immunophenotyping; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D013045:Species Specificity; D013953:Thymus Neoplasms / Q000235:genetics*