A genome-wide screen for genetic alterations in radiationinduced thymic lymphomas generated fromp53+/− andp53−/− mice showed frequent loss of heterozygosity (LOH) on chromosome 6. Fine mapping of these LOH regions revealed three non-overlapping regions, one of which was refined to a 0.2 Mb interval that contained only the gene encoding homeobox-interacting protein kinase 2 (Hipk2). More than 30% of radiation-induced tumors from bothp53+/− andp53−/− mice showed heterozygous loss of oneHipk2allele. Mice carrying a single inactive allele ofHipk2in the germline were susceptible to induction of tumors by γ-radiation, but most tumors retained and expressed the wild-type allele, suggesting thatHipk2is a haploinsufficient tumor suppressor gene for mouse lymphoma development. Heterozygous loss of bothHipk2andp53confers strong sensitization to radiation-induced lymphoma. We conclude thatHipk2is a haploinsufficient lymphoma suppressor gene.
Oncogene (2012) 31, 1176–1180; doi:10.1038/onc.2011.306; published online 25 July 2011