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  • Oncogenomics
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Gene expression and copy number profiling suggests the importance of allelic imbalance in 19p in asbestos-associated lung cancer

Oncogene volume 26, pages 4730–4737 (2007)Cite this article

Abstract

Asbestos is a pulmonary carcinogen known to give rise to DNA and chromosomal damage, but the exact carcinogenic mechanisms are still largely unknown. In this study, gene expression arrays were performed on lung tumor samples from 14 heavily asbestos-exposed and 14 non-exposed patients matched for other characteristics. Using a two-step statistical analysis, 47 genes were revealed that could differentiate the tumors of asbestos-exposed from those of non-exposed patients. To identify asbestos-associated regions with DNA copy number and expressional changes, the gene expression data were combined with comparative genomic hybridization microarray data. As a result, a combinatory profile of DNA copy number aberrations and expressional changes significantly associated with asbestos exposure was obtained. Asbestos-related areas were detected in 2p21–p16.3, 3p21.31, 5q35.2–q35.3, 16p13.3, 19p13.3–p13.1 and 22q12.3–q13.1. The most prominent of these, 19p13, was further characterized by microsatellite analysis in 62 patients for the differences in allelic imbalance (AI) between the two groups of lung tumors. 79% of the exposed and 45% of the non-exposed patients (P=0.008) were found to be carriers of AI in their lung tumors. In the exposed group, AI in 19p was prevalent regardless of the histological tumor type. In adenocarcinomas, AI in 19p appeared to occur independently of the asbestos exposure.

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Abbreviations

CGH array:

comparative genomic hybridization array

LOH:

loss of heterozygosity

AI:

allelic imbalance

MSI:

microsatellite instability

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Acknowledgements

We are grateful to Mrs Päivi Tuominen and Mrs Tuula Stjernvall for excellent technical assistance. We also thank Mrs Helinä Urhonen and Dr Kaisa Salmenkivi for helping with collecting the samples. This work is financially supported by the Academy of Finland Grants 200802 and 207469, Finnish Cancer Foundations, Sigrid Jusélius Foundation, Finnish Work Environment Fund Grant 102125, and Graduate school in Computational Biology, Bioinformatics and Biometry.

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Author notes

  1. H Wikman and S Ruosaari: These two authors equally contributed to this work.

Authors and Affiliations

  1. Finnish Institute of Occupational Health, Helsinki, Finland

    H Wikman, S Ruosaari, P Nymark, V K Sarhadi, E Vanhala, A Karjalainen & S Anttila

  2. Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    H Wikman

  3. Laboratory of Computer and Information Science, Helsinki University of Technology, Espoo, Finland

    S Ruosaari & J Hollmén

  4. Department of Pathology, Haartman Institute, University of Helsinki, and HUSLAB, Helsinki University Central Hospital, Helsinki, Finland

    S Ruosaari, P Nymark, S Knuutila & S Anttila

  5. Department of Molecular Medicine, National Public Health Institute, Biomedicum, Helsinki, Finland

    J Saharinen

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  1. H Wikman
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  2. S Ruosaari
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Correspondence to S Anttila.

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

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Wikman, H., Ruosaari, S., Nymark, P. et al. Gene expression and copy number profiling suggests the importance of allelic imbalance in 19p in asbestos-associated lung cancer. Oncogene 26, 4730–4737 (2007). https://doi.org/10.1038/sj.onc.1210270

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