KU70 - A CANDIDATE TUMOR-SUPPRESSOR GENE FOR MURINE T-CELL LYMPHOMA

We present evidence that inactivation of the Ku70 gene leads to a prop ensity for malignant transformation both in vitro and in vivo. In vitr o, Ku70(-/-) mouse fibroblasts displayed an increased rate of sister c hromatid exchange and a high frequency of spontaneous neoplastic trans formation. In vivo, Ku70(-/-) mice, known to be defective in B but not T lymphocyte maturation, developed thymic and disseminated T cell lym phomas at a mean age of 6 months with CD4(+)CD8(+) tumor cells. These findings directly demonstrate that Ku70 deficiency facilitates neoplas tic growth and suggest a novel role of the Ku70 locus in tumor suppres sion.