ATM-deficient Thymic Lymphoma is Associated with Aberrant tcrd Rearrangement and Gene Amplification

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ATM-deficient Thymic Lymphoma is Associated with Aberrant tcrd Rearrangement and Gene Amplification

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Title: ATM-deficient Thymic Lymphoma is Associated with Aberrant tcrd Rearrangement and Gene Amplification
Author: Bassing, Craig H.; Brush, James W.; Patel, Harin; Goff, Peter H.; Gatti, Richard A.; Zha, Shan; Sanda, Takaomi; Murphy, Michael M.; Tepsuporn, Suprawee; Look, A. Thomas; Alt, Frederick W.

Note: Order does not necessarily reflect citation order of authors.

Citation: Zha, Shan, Craig H. Bassing, Takaomi Sanda, James W. Brush, Harin Patel, Peter H. Goff, Michael M. Murphy, et al. 2010. ATM-deficient thymic lymphoma is associated with aberrant tcrd rearrangement and gene amplification. The Journal of Experimental Medicine 207(7): 1369-1380.
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Abstract: Ataxia telangiectasia mutated (ATM) deficiency predisposes humans and mice to T lineage lymphomas with recurrent chromosome 14 translocations involving the T cell receptor α/δ (Tcra/d) locus. Such translocations have been thought to result from aberrant repair of DNA double-strand breaks (DSBs) during Tcra locus V(D)J recombination, and to require the Tcra enhancer (Eα) for Tcra rearrangement or expression of the translocated oncogene. We now show that, in addition to the known chromosome 14 translocation, ATM-deficient mouse thymic lymphomas routinely contain a centromeric fragment of chromosome 14 that spans up to the 5′ boundary of the Tcra/d locus, at which position a 500-kb or larger region centromeric to Tcra/d is routinely amplified. In addition, they routinely contain a large deletion of the telomeric end of one copy of chromosome 12. In contrast to prior expectations, the recurrent translocations and amplifications involve V(D)J recombination–initiated breaks in the Tcrd locus, as opposed to the Tcra locus, and arise independently of the Eα. Overall, our studies reveal previously unexpected mechanisms that contribute to the oncogenic transformation of ATM-deficient T lineage cells.
Published Version: doi:10.1084/jem.20100285
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2901073/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4866478

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