Cancer in humans is typically a very heterogeneous disease and it is thus difficult to analyse genetically. One of the main thrusts of cancer research over the past 25 years has been to identify genes that are mutated in cancer. The Bradley laboratory is interested in performing one of the largest comprehensive analyses of the and 'cancer genome and" in a cancer prone mouse model: irradiated bloom deficient mice. Loss of the DNA helicase Bloom function has been described in human Bloom syndrome and leads to a breakdown in the maintenance of genome integrity, in particular hyper-recombination and cancer predisposition. This gene has been knocked out in mice by the Bradley lab, and like in the human syndrome, bloom deficient mice are cancer prone in a wide variety of different cell types including carcinomas, sarcomas and lymphomas. Thus, this model provides an opportunity to identify genomic regions or genes that are frequently rearranged in cancer. The laboratory has developed an automated method to generate a genome wide molecular profile of a tumour in a single experiment using BAC-CGH arrays (comparative genomic hybridisation). Analysis of tumour DNA extracted from Bloom mouse cancer model will provide information of frequent deleted and amplified region. This study requires the analysis of hundreds of tumours and comparisons of rearrangements from tumours of the same types. Identification of sites of rearrangements will be useful in order to identify new genes involved in cancer. Once identified, these genes could be deleted in mice in order to evaluate their potential function in cancer. This will yield potential new diagnostic opportunities and perhaps might suggest new therapeutic approaches.
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