Oncogenomics

Oncogene (2006) 25, 7324–7332. doi:10.1038/sj.onc.1209717; published online 5 June 2006

DNA copy number amplification profiling of human neoplasms

S Myllykangas1, J Himberg2, T Böhling1, B Nagy1,3, J Hollmén2 and S Knuutila1

  1. 1Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
  2. 2Laboratory of Computer and Information Science, Helsinki University of Technology, Espoo, Finland
  3. 31st Department of Obstetrics and Gynecology, Scmmclwcis University, Budapest, Hungary

Correspondence: S Myllykangas, Department of Pathology, Haartman Institute, University of Helsinki, PO Box 21, FI-00014 Helsinki, Finland. E-mail: samuel.myllykangas@helsinki.fi

Received 1 February 2006; Revised 13 April 2006; Accepted 20 April 2006; Published online 5 June 2006.

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Abstract

DNA copy number amplifications activate oncogenes and are hallmarks of nearly all advanced tumors. Amplified genes represent attractive targets for therapy, diagnostics and prognostics. To investigate DNA amplifications 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 amplified 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 overrepresented on the fragile sites and the reported amplification hot spots. These findings indicate that amplifications are selected in the cancer tissue environment according to the qualitative traits and localization of cancer genes.

Keywords:

cancer, gene amplification, fragile site, bioinformatics, data mining, molecular pathology

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