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Title: An investigation of tumour susceptibility in a modified ATM-/- mouse with no thymoma risk
Author: Francis, Tegan Adeline
ISNI:       0000 0004 5359 5300
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2015
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Ataxia telangiectasia (A-T) is characterised by a predisposition to the development of a range of lymphoid tumours of both T and B cell origin. Currently, Atm-/- mice develop an aggressive thymic lymphoma and die by 13 weeks of age. In order to overcome this barrier to long lived mice and expand the range of lymphoid tumours driven by Atm loss, I crossed the Atm-/- mouse with the nude mouse (nu-/-). The resulting Atm-/-nu-/- mice had a greater lifespan compared to the Atm-/- mice (median survival of 175 days versus 91 days). Of 17/69 Atm-/-nu-/- mice that developed a tumour sixteen were of B cell origin occurring in the spleen, liver, gut and axillary nodes. Histological examination of the B cell-derived tumours revealed that they were phenotypically heterogeneous. No tumours were observed in the control mice (Atm+/+nu-/- or Atm+/+nu+/-). Fluorescence in situ hybridisation (FISH) revealed the presence of IgH translocations in 1/6 B cell lymphomas and 2/6 tumours had an additional copy of Myc. M-FISH revealed clonal abnormalities involving chromosomes 17 and/or 18 in 5/6 tumours analysed. We conclude that in contrast to T cell lymphoma development in Atm-/- mice, which is associated with immune gene translocations and Myc amplification, the Atm-/-nu-/- model of A-T gives B cell lymphomas arising at different stages of B cell development and may be more representative of the types of B cell lymphoma in patients with A-T.
Supervisor: Not available Sponsor: Cancer Research UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC0254 Neoplasms. Tumors. Oncology (including Cancer)