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1 April 2008 Analysis of Changes in DNA Copy Number in Radiation-Induced Thymic Lymphomas of Susceptible C57BL/6, Resistant C3H and Hybrid F1 Mice
Takashi Takabatake, Shizuko Kakinuma, Tokuhisa Hirouchi, Masako M. Nakamura, Katsuyoshi Fujikawa, Mayumi Nishimura, Yoichi Oghiso, Yoshiya Shimada, Kimio Tanaka
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Abstract

Takabatake, T., Kakinuma, S., Hirouchi, T., Nakamura, M. M., Fujikawa, K., Nishimura, M., Oghiso, Y., Shimada, Y. and Tanaka, K. Analysis of Changes in DNA Copy Number in Radiation-Induced Thymic Lymphomas of Susceptible C57BL/6, Resistant C3H and Hybrid F1 Mice. Radiat. Res. 169, 426–435 (2008).

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 F1 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.

Takashi Takabatake, Shizuko Kakinuma, Tokuhisa Hirouchi, Masako M. Nakamura, Katsuyoshi Fujikawa, Mayumi Nishimura, Yoichi Oghiso, Yoshiya Shimada, and Kimio Tanaka "Analysis of Changes in DNA Copy Number in Radiation-Induced Thymic Lymphomas of Susceptible C57BL/6, Resistant C3H and Hybrid F1 Mice," Radiation Research 169(4), 426-436, (1 April 2008). https://doi.org/10.1667/RR1180.1
Received: 2 August 2007; Accepted: 1 November 2007; Published: 1 April 2008
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