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Microarray analyses reveal strong influence of DNA copy number alterations on the transcriptional patterns in pancreatic cancer: implications for the interpretation of genomic amplifications

Oncogene volume 24, pages 1794–1801 (2005)Cite this article

Abstract

DNA copy number alterations are believed to play a major role in the development and progression of human neoplasms. Although most of these genomic imbalances have been associated with dysregulation of individual genes, their large-scale transcriptional consequences remain unclear. Pancreatic carcinomas frequently display gene copy number variation of entire chromosomes as well as of chromosomal subregions. These changes range from homozygous deletions to high-level amplifications and are believed to constitute key genetic alterations in the cellular transformation of this tumor type. To investigate the transcriptional consequences of the most drastic genomic changes, that is, genomic amplifications, and to analyse the genome-wide transcriptional effects of DNA copy number changes, we performed expression profiling of 29 pancreatic carcinoma cell lines and compared the results with matching genomic profiling data. We show that a strong association between DNA copy numbers and mRNA expression levels is present in pancreatic cancer, and demonstrate that as much as 60% of the genes within highly amplified genomic regions display associated overexpression. Consequently, we identified 67 recurrently overexpressed genes located in seven precisely mapped commonly amplified regions. The presented findings indicate that more than one putative target gene may be of importance in most pancreatic cancer amplicons.

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Acknowledgements

This work was supported by the Swedish Cancer Society, the American Cancer Society, the EC COST Action B19, the Crafoord Foundation, the John and Augusta Persson Foundation, the Eric Philip Sörensen Foundation, and the Royal Physiographic Society.

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Authors and Affiliations

  1. Department of Clinical Genetics, Lund University Hospital, SE-221 85, Lund, Sweden

    Markus Heidenblad, David Lindgren, Tord Jonson, Ludmila Gorunova & Mattias Höglund

  2. Department of Human Genetics, University Medical Center Nijmegen, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

    Joris A Veltman, Ad Geurts van Kessel & Eric F P M Schoenmakers

  3. Laboratory of Cancer Genetics, University of Tampere and Tampere University Hospital, Tampere, Finland

    Eija H Mahlamäki

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  1. Markus Heidenblad
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Correspondence to Markus Heidenblad.

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Supplementary Information accompanies the paper on Oncogene website (http://www.nature.com/onc)

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Heidenblad, M., Lindgren, D., Veltman, J. et al. Microarray analyses reveal strong influence of DNA copy number alterations on the transcriptional patterns in pancreatic cancer: implications for the interpretation of genomic amplifications. Oncogene 24, 1794–1801 (2005). https://doi.org/10.1038/sj.onc.1208383

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