Enhanced tumor formation in mice heterozygous for Blm mutation.
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.
Goss
Kathleen Heppner
KH
Department of Department of Molecular Genetics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
Risinger
Mary A
MA
Kordich
Jennifer J
JJ
Sanz
Maureen M
MM
Straughen
Joel E
JE
Slovek
Lisa E
LE
Capobianco
Anthony J
AJ
German
James
J
Boivin
Gregory P
GP
Groden
Joanna
J
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
D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases