Cancer predisposition caused by elevated mitotic recombination in Bloom mice

Bloom syndrome is a disorder associated with genomic instability that cause s affected people to be prone to cancer. Bloom cell lines show increased si ster chromatid exchange, yet are proficient in the repair of various DNA le sions. The underlying cause of this disease are mutations in a gene encodin g a RECQ DNA helicase. Using embryonic stem cell technology, we have genera ted viable Bloom mice that are prone to a wide variety of cancers. Cell lin es from these mice show elevations in the rates of mitotic recombination. W e demonstrate that the increased rate of loss of heterozygosity (LOH) resul ting from mitotic recombination in vivo constitutes the underlying mechanis m causing tumour susceptibility in these mice.