DNA ligase IV suppresses medulloblastoma formation.

Lee, Youngsoo; McKinnon, Peter J · Cancer Res · 2002

basic_science · Level V

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Abstract

Substantial neural defects are often present in mice with targeted inactivation of DNA repair factors such as DNA ligase IV (Lig4). Whereas Lig4(-/-) mice undergo widespread neural apoptosis and die during development, p53 deficiency rescues this death. We found that all Lig4(-/-)p53(-/-) mice developed medulloblastoma, but did not develop other tumors of the nervous system. Lig4(-/-)p53(-/-) medulloblastoma occurred as early as 21 days of age, originated in the external granule layer of the developing cerebellum, and was synaptophysin immunoreactive. These data reveal a pronounced susceptibility of the cerebellum to the effects of chronic DNA damage and provide a direct link between genotoxic stress and medulloblastoma formation.

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