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We are studying the “cancer genome” 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 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 cancerWe analyzed a cohort of T lymphoblastic lymphoma primary cell lines derived from the cancer prone Bloom deficient mice using high resolution array CGH and multicolor FISH (collaboration with N- Carter’s group). We discovered, among other alterations in these samples, that the distal part of chromosome 12 was frequently rearranged ( ie deleted or amplified as seen in aCGH and/or translocated seen in MFISH). Chr12 is often involved in balanced and unbalanced translocations in T-lymphoma with different partners (ie:1, 5, 14, 15, 16 and 17) and show frequent rearrangements around E-F2 band (deletion and/or amplifications). Using aCGH and FISH, we were able to map some of these rearrangements and found that a sub-region around 108Mb on chromosome 12 was frequently targeted. • In the cases of unbalanced translocations, in 30% of the cases chromosome 12 breakpoints occur more frequently around 108Mb within a 2.5Mb window (n=15).• In the cases of the balanced translocations, chromosome 12 breakpoints occur within 55Kb around 108Mb in a genomic desert (n=2).• In the cases of the rearrangements on chromosome 12, translocation independent, a 60kb minimum common region containing Bcl11b gene was identified (n=6). We think that the targeted gene in our lymphoma is Bcl11b which is a well know tumour suppressor gene in lymphoma. This gene could be either deleted (by deletion or translocation) or its regulatory element(s) misplaced in the cases of balanced translocations. We need to use genome wide parallel pair-ended sequencing to map more precisely some of the complex breakpoints we have in the balanced and unbalanced translocations involving chromosome 12. Furthermore, we would like to eventually identify any fusion transcript which could arise from these translocations.. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ |