Alt, Frederick W.Tepsuporn, Suprawee2014-02-252014-02-252013Tepsuporn, Suprawee. 2013. Role of ATM in Suppressing Oncogenic Translocations and Mature B Cell Lymphomas. Doctoral dissertation, Harvard University.http://dissertations.umi.com/gsas.harvard:11230http://nrs.harvard.edu/urn-3:HUL.InstRepos:11744426The ATM protein senses DNA double-stranded breaks (DSBs) and facilitates proper repair. B and T lymphocytes of ATM-deficient patients have increased antigen receptor locus translocations associated with aberrant V(D)J recombination. Correspondingly, ATM-deficient humans are predisposed to both T and B cell malignancies. However, ATM-deficiency in mice only leads to T cell lymphomas, all of which harbor T cell receptor locus translocations resulting from aberrant V(D)J recombination. The first goal of this study was to assess whether ATM-deficient B cell lymphomas occur in mice in which V(D)J recombination is targeted to the c-myc oncogene or in which B cell survival is increased via enforced expression of the anti-apoptotic Bcl2 protein. We found that, in the absence of ATM, either inserting the V(D)J substrate into c-myc or enhancing B cell survival led to the development of mature B cell lymphomas in a subset of mice. Moreover, combining both genetic alterations led to complete penetrance of mature B cell lymphomas in the ATM-deficient background.en-USImmunologyThesis or Dissertation2015-02-04