期刊
ONCOGENE
卷 25, 期 55, 页码 7324-7332出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1209717
关键词
cancer; gene amplification; fragile site; bioinformatics; data mining; molecular pathology
DNA copy number amplications activate oncogenes and are hallmarks of nearly all advanced tumors. Amplified genes represent attractive targets for therapy, diagnostics and prognostics. To investigate DNA amplications in different neoplasms, we performed a bibliomics survey using 838 published chromosomal comparative genomic hybridization studies and collected amplification data at chromosome band resolution from more than 4500 cases. Amplification profiles were determined for 73 distinct neoplasms. Neoplasms were clustered according to the amplification profiles, and frequently amplificed chromosomal loci (amplification hot spots) were identified using computational modeling. To investigate the site specificity and mechanisms of gene amplifications, colocalization of amplification hot spots, cancer genes, fragile sites, virus integration sites and gene size cohorts were tested in a statistical framework. Amplification-based clustering demonstrated that cancers with similar etiology, cell-of-origin or topographical location have a tendency to obtain convergent amplification profiles. The identified amplification hot spots were colocalized with the known fragile sites, cancer genes and virus integration sites, but global statistical significance could not be ascertained. Large genes were significantly over-represented on the fragile sites and the reported amplifcation hot spots. These findings indicate that amplifications are selected in the cancer tissue environment according to the qualitative traits and localization of cancer genes.
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