title: Hipk2 cooperates with p53 to suppress γ-ray radiation-induced mouse thymic lymphoma.
abstract: A genome-wide screen for genetic alterations in radiation-induced thymic lymphomas generated from p53+/- and p53-/- 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 both p53+/- and p53-/- mice showed heterozygous loss of one Hipk2 allele. Mice carrying a single inactive allele of Hipk2 in the germline were susceptible to induction of tumors by γ-radiation, but most tumors retained and expressed the wild-type allele, suggesting that Hipk2 is a haploinsufficient tumor suppressor gene for mouse lymphoma development. Heterozygous loss of both Hipk2 and p53 confers strong sensitization to radiation-induced lymphoma. We conclude that Hipk2 is a haploinsufficient lymphoma suppressor gene.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: J-H
authors.initials: JH
authors.lastname: Mao
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: I-J
authors.initials: IJ
authors.lastname: Kim
authors.forename: H C
authors.initials: HC
authors.lastname: Kang
authors.forename: G
authors.initials: G
authors.lastname: Wei
authors.forename: J
authors.initials: J
authors.lastname: Climent
authors.forename: A
authors.initials: A
authors.lastname: Kumar
authors.forename: F G
authors.initials: FG
authors.lastname: Pelorosso
authors.forename: R
authors.initials: R
authors.lastname: DelRosario
authors.forename: E J
authors.initials: EJ
authors.lastname: Huang
authors.forename: A
authors.initials: A
authors.lastname: Balmain
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D033481:Chromosomes, Mammalian; D005720:Gamma Rays / Q000009:adverse effects*; D015972:Gene Expression Regulation, Neoplastic; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013953:Thymus Neoplasms / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D016159:Tumor Suppressor Protein p53; C492003:Hipk2 protein, mouse; D017346:Protein Serine-Threonine Kinases