Abstract
Loss of heterozygosity (LOH) analysis, performed in 68 γ-radiation-induced primary thymic lymphomas of F1 hybrid mice, provided evidence of significant LOH on chromosome 19 in a region defined by the D19Mit106 (22 cM) and D19Mit100 (27 cM) markers (Thymic Lymphoma Suppressor Region 8, TLSR8). Cd95 and Pten, two genes mapped at this region, were inactivated in a vast majority of these tumors (85.3% for Cd95 and 61.8% for Pten). Moreover, altered expression of Cd95 and Pten occurred concomitantly in 34 of 68 (50%) thymic lymphomas suggesting a coordinated mechanism of inactivation of these genes. Surprisingly, we also found that Jak2, a proto-oncogene located between Cd95 and Pten, was simultaneously inactivated in a significant fraction of the tumors analysed (24 of 34, 70.6%). Taken together these findings and the lack of mutations in the coding sequences of the mentioned genes clearly suggest a possible regional epigenetic inactivation mechanism on mouse chromosome 19 operating during the development of these tumors.
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Acknowledgements
This work was supported in part by grants PM99/003 (Ministerio Educación y Cultura, Spain) and 08/0043/1998 (Comunidad Autónoma de Madrid, Spain) to J Fernández-Piqueras, and BMH4-98-3426 (BIOMED 2 program, European Union) and 08/0008/1999 (Comunidad Autónoma de Madrid, Spain) to J Santos.
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Santos, J., Herranz, M., Fernández, M. et al. Evidence of a possible epigenetic inactivation mechanism operating on a region of mouse chromosome 19 in γ-radiation-induced thymic lymphomas. Oncogene 20, 2186–2189 (2001). https://doi.org/10.1038/sj.onc.1204297
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DOI: https://doi.org/10.1038/sj.onc.1204297
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