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Recurrent genetic alterations in thymic lymphomas of LckMyrAkt2 transgenic mice

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Description: The LckMyrAkt2 transgenic mouse is a murine model in which overexpression of a constitutively active form of Akt2 (myristylated Akt2) is targeted specifically to developing T cells localized in the thymus. Consistent with Akt's role as a proto-oncogene, transgenic mice that overexpress constitutively activated Akt2 develop thymic lymphomas. The focus of my thesis was to characterize the cytogenetic alterations seen in thymic lymphomas arising in three founder lines of Lck MyrAkt2 mice. Founder 420 exhibited a consistent inversion of chromosome 6, while founder 72 exhibited a consistent translocation involving chromosomes 14 and 15. The alterations in a third founder line were variable, with some tumors exhibiting the 14/15 translocation and one showing inversion 6. The rearrangements are clonal and recurrent, suggesting that they are important events in tumor formation and could potentially co-operate with Akt2 in oncogenesis. Therefore, the breakpoints of the inversion and translocation were determined using fluorescence in situ hybridization (FISH), and found to involve the T cell receptor loci in all cases. (Abstract shortened by UMI.)
Language: English
Format: Degree Work