title: Enhanced tumor formation in mice heterozygous for Blm mutation.
abstract: Persons with the autosomal recessive disorder Bloom syndrome are predisposed to cancers of many types due to loss-of-function mutations in the BLM gene, which encodes a recQ-like helicase. Here we show that mice heterozygous for a targeted null mutation of Blm, the murine homolog of BLM, develop lymphoma earlier than wild-type littermates in response to challenge with murine leukemia virus and develop twice the number of intestinal tumors when crossed with mice carrying a mutation in the Apc tumor suppressor. These observations indicate that Blm is a modifier of tumor formation in the mouse and that Blm haploinsufficiency is associated with tumor predisposition, a finding with important implications for cancer risk in humans.
authors.affiliation: Department of Department of Molecular Genetics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
authors.forename: Kathleen Heppner
authors.initials: KH
authors.lastname: Goss
authors.forename: Mary A
authors.initials: MA
authors.lastname: Risinger
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Kordich
authors.forename: Maureen M
authors.initials: MM
authors.lastname: Sanz
authors.forename: Joel E
authors.initials: JE
authors.lastname: Straughen
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Slovek
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Capobianco
authors.forename: James
authors.initials: J
authors.lastname: German
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Boivin
authors.forename: Joanna
authors.initials: J
authors.lastname: Groden
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000483:Alleles; D000818:Animals; D001816:Bloom Syndrome / Q000235:genetics*; D002478:Cells, Cultured; D003433:Crosses, Genetic; D004265:DNA Helicases / Q000235:genetics*; D005260:Female; D018390:Gene Targeting; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D009052:Leukemia Virus, Murine; D019656:Loss of Heterozygosity; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D053484:RecQ Helicases; D012854:Sister Chromatid Exchange
chemical_list: D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases