tailieunhanh - Báo cáo y học: "Somatic structural rearrangements in genetically engineered mouse mammary tumors"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Somatic structural rearrangements in genetically engineered mouse mammary tumors. | Varela et al. Genome Biology 2010 11 R100 http 2010 11 10 R100 w Genome Biology RESEARCH Open Access Somatic structural rearrangements in genetically engineered mouse mammary tumors 1 23 1 1 1 Ignacio Varela Christiaan Klijn Phillip J Stephens Laura J Mudie Lucy Stebbings Danushka Galappaththige1 Hanneke van der Gulden2 Eva Schut2 Sjoerd Klarenbeek2 Peter J Campbell1 23 14 2 1 1 Lodewyk FA Wessels Michael R Stratton Jos Jonkers P Andrew Futreal David J Adams Abstract Background Here we present the first paired-end sequencing of tumors from genetically engineered mouse models of cancer to determine how faithfully these models recapitulate the landscape of somatic rearrangements found in human tumors. These were models of Trp53-mutated breast cancer Brcal- and Brca2-associated hereditary breast cancer and E-cadherin Cdh1 mutated lobular breast cancer. Results We show that although Brcal- and Brca2-deficient mouse mammary tumors have a defect in the homologous recombination pathway there is no apparent difference in the type or frequency of somatic rearrangements found in these cancers when compared to other mouse mammary cancers and tumors from all genetic backgrounds showed evidence of microhomology-mediated repair and non-homologous end-joining processes. Importantly mouse mammary tumors were found to carry fewer structural rearrangements than human mammary cancers and expressed in-frame fusion genes. Like the fusion genes found in human mammary tumors these were not recurrent. One mouse tumor was found to contain an internal deletion of exons of the Lrplb gene which led to a smaller in-frame transcript. We found internal in-frame deletions in the human ortholog of this gene in a significant number of human cancer cell lines. Conclusions Paired-end sequencing of mouse mammary tumors revealed that they display significant heterogeneity in their profiles of somatic rearrangement but importantly fewer rearrangements than cognate human mammary .