tailieunhanh - báo cáo khoa học: " High-throughput analysis of chromosome translocations and other genome rearrangements in epithelial cancers"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: High-throughput analysis of chromosome translocations and other genome rearrangements in epithelial cancers | Newman and Edwards Genome Medicine 2010 2 19 http content 2 3 19 w Genome Medicine MINIREVIEW L__ High-throughput analysis of chromosome translocations and other genome rearrangements in epithelial cancers Scott Newman and Paul AW Edwards Abstract Genes that are broken or fused by structural changes to the genome are an important class of mutation in the leukemias and sarcomas but have been largely overlooked in the common epithelial cancers. Large-scale sequencing is changing our perceptions of the cancer genome and it is now being applied to structural changes using the paired end strategy. This reveals more clearly than before the extent to which many cancer genomes are rearranged and how much these rearrangements contribute to the mutational burden of epithelial tumors. In particular there are probably many fusion genes analogous to those found in leukemias to be found in common cancers such as breast carcinoma and some of these will prove to be important in cancer diagnosis and treatment. Introduction Somatic structural variations in the genome - referred to by cytogeneticists as translocations inversions duplications and insertions - can be powerful events in tumor evolution because they can create fusion genes. Fusion genes are formed when part of one gene is juxtaposed to another by a structural rearrangement creating a hybrid transcript or sometimes simply inserting a novel promoter upstream of a gene. These can be very powerful oncogenic mutations not only increasing expression of a protein but also changing its activity subcellular localization or binding specificity 1 2 . Such fusion genes are also clinically important because some can predict outcome and determine management and some may be targets for therapy 1 . For example the BCR-ABL fusion gene defines a group of leukemias and is the target of treatment with the kinase inhibitor Glivec. Correspondence sn353@ pawe1@ Hutchison-MRC Research Centre and .

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