Recurrent chromosomal rearrangements implicate oncogenes contributing to T-cell lymphomagenesis in Lck-MyrAkt2 transgenic mice.
Recurrent chromosomal rearrangements implicate oncogenes contributing to T-cell lymphomagenesis in Lck-MyrAkt2 transgenic mice.
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DOI：
10.1002/gcc.20683
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Testa JR
中科院分区：
文献类型：
--
作者：
Timakhov RA;Tan Y;Rao M;Liu Z;Altomare DA;Pei J;Wiest DL;Favorova OO;Knepper JE;Testa JR
The oncogene v-akt was isolated from a retrovirus that induced naturally occurring thymic lymphomas in AKR mice. We hypothesized that constitutive activation of Akt2 could serve as a first hit for the clonal expansion of malignant T-cells by promoting cell survival and genomic instability, leading to chromosome alterations. Furthermore, genes that cooperate with Akt2 to promote malignant transformation may reside at translocation/inversion junctions found in spontaneous thymic lymphomas from transgenic mice expressing constitutively active Akt2 specifically in T cells. Cytogenetic analysis revealed that thymic tumors from multiple founder lines exhibited either of two recurrent chromosomal rearrangements, inv(6)(A2B1) or t(14;15)(C2;D1). Fluorescence in situ hybridization, array-CGH, and PCR analysis was used to delineate the inv(6) and t(14;15) breakpoints. Both rearrangements involved T-cell receptor loci. The inv(6) results in robust up regulation of the homeobox/transcription factor gene Dlx5 due to its relocation near the Tcrb enhancer. The t(14;15) places the Tcra enhancer in the vicinity of the Myc proto-oncogene, resulting in up regulated Myc expression. These findings suggest that activation of the Akt pathway can act as the initial hit to promote cell survival and genomic instability, while the acquisition of T-cell-specific overexpression of Dlx5 or Myc leads to lymphomagenesis.
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DOI：
10.1073/pnas.231467698
发表时间：
2001-12-18
影响因子：
11.1
作者：
Malstrom, S;Tili, E;Tsichlis, PN
通讯作者：
Tsichlis, PN
影响因子：
8
作者：
Rabbitts, TH
通讯作者：
Rabbitts, TH
影响因子：
56.9
作者：
Gaudet, F;Hodgson, JG;Jaenisch, R
通讯作者：
Jaenisch, R
影响因子：
8
作者：
Mende, I;Malstrom, S;Aoki, M
通讯作者：
Aoki, M
影响因子：
56.9
作者：
Look, AT
通讯作者：
Look, AT