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Science 20 September 2002:
Vol. 297. no. 5589, pp. 2051 - 2053
DOI: 10.1126/science.1074340

Reports

Enhanced Tumor Formation in Mice Heterozygous for Blm Mutation

Kathleen Heppner Goss, Mary A. Risinger, Jennifer J. Kordich, Maureen M. Sanz, Joel E. Straughen, Lisa E. Slovek, Anthony J. Capobianco, James German, Gregory P. Boivin, Joanna Groden

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.


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