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[Cancer Research 62, 6395-6399, November 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

DNA Ligase IV Suppresses Medulloblastoma Formation1

Youngsoo Lee and Peter J. McKinnon2

Department of Genetics, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105

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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Copyright © 2002 by the American Association for Cancer Research.