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Báo cáo y học: " Analysis of the copy number profiles of several tumor samples from the same patient reveals the successive steps in tumorigenesis"

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: Analysis of the copy number profiles of several tumor samples from the same patient reveals the successive steps in tumorigenesis. | Letouze et al. Genome Biology 2010 11 R76 http genomebiology.eom 2010 11 7 R76 Genome Biology METHOD Open Access Analysis of the copy number profiles of several tumor samples from the same patient reveals the successive steps in tumorigenesis 1.2.3 4.5 6 2.3 I- I 1 Eric Letouze 1 Yves Allory Marc A Bollet Frangois Radvanyi Frédéric Guyon Abstract We present a computational method TuMult for reconstructing the sequence of copy number changes driving carcinogenesis based on the analysis of several tumor samples from the same patient. We demonstrate the reliability of the method with simulated data and describe applications to three different cancers showing that TuMult is a valuable tool for the establishment of clonal relationships between tumor samples and the identification of chromosome aberrations occurring at crucial steps in cancer progression. Background It is now widely accepted that cancers arise from an accumulation of genetic and epigenetic alterations through which cells acquire the properties required for malignancy 1 . These alterations - mutations chromosomal aberrations and aberrant DNA methylation - are inherently random and undirected consistent with a model of clonal evolution 2 in which advanced tumors result from the clonal expansion of a single cell of origin and the sequential selection of sublines with additional alterations conferring a growth advantage. As a result the tumor finally detected in clinical conditions usually displays a complex pattern of genetic alterations. As we generally only have data for a single time point in cancer progression the time of surgery the standard approach to elucidating the various steps in tumorigen-esis has been to compare genetic alterations in tumors from different patients with cancers of different histological stages and grades. Early alterations are defined as changes observed at all stages whereas late events are alterations associated exclusively with advanced stages. The first model of the .