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  • Oncogenomics
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Gene-expression profiling reveals distinct expression patterns for Classic versus Variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma

Oncogene volume 23, pages 2732–2742 (2004)Cite this article

Abstract

Merkel cell carcinoma (MCC) is a rare aggressive skin tumor which shares histopathological and genetic features with small-cell lung carcinoma (SCLC), both are of neuroendocrine origin. Comparable to SCLC, MCC cell lines are classified into two different biochemical subgroups designated as ‘Classic’ and ‘Variant’. With the aim to identify typical gene-expression signatures associated with these phenotypically different MCC cell lines subgroups and to search for differentially expressed genes between MCC and SCLC, we used cDNA arrays to profile 10 MCC cell lines and four SCLC cell lines. Using significance analysis of microarrays, we defined a set of 76 differentially expressed genes that allowed unequivocal identification of Classic and Variant MCC subgroups. We assume that the differential expression levels of some of these genes reflect, analogous to SCLC, the different biological and clinical properties of Classic and Variant MCC phenotypes. Therefore, they may serve as useful prognostic markers and potential targets for the development of new therapeutic interventions specific for each subgroup. Moreover, our analysis identified 17 powerful classifier genes capable of discriminating MCC from SCLC. Real-time quantitative RT–PCR analysis of these genes on 26 additional MCC and SCLC samples confirmed their diagnostic classification potential, opening opportunities for new investigations into these aggressive cancers.

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Acknowledgements

This work was supported by GOA Grant 12051397, FWO Grant G.0028.00 and the Queensland Cancer Fund and the Queensland Radium Institute Research Unit. Anthony L Cook is supported by a University of Queensland Mid Year Scholarship. Jo Vandesompele is sponsored by VEO-grant 011V1302. Nadine Van Roy is a postdoctoral researcher of the Fund for Scientific Research, Flanders. This paper presents the research results of the Belgian program of Interuniversity Poles of attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. The scientific responsibility is assumed by us. We would like to thank Drs MM Hughes, VM Hinkley, RW Allison, W Cockborn, TJ Harris and O Williams for their support in collecting the Queensland MCC specimens, from which the MCC cell lines were established, and H Salwen for providing MCC cell line MKL-2.

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Authors and Affiliations

  1. Center for Medical Genetics, Ghent University Hospital, Ghent, B-9000, Belgium

    Mireille Van Gele, Jo Vandesompele, Nadine Van Roy, Anne De Paepe & Frank Speleman

  2. Melanoma Genomics Group, Queensland Institute of Medical Research, Brisbane, 4006, Queensland, Australia

    Glen M Boyle & Peter G Parsons

  3. Institute for Molecular Biosciences, University of Queensland, Brisbane, 4072, Queensland, Australia

    Anthony L Cook

  4. Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and University of Ghent, Ghent, B-9000, Belgium

    Tom Boonefaes & Pieter Rottiers

  5. Queensland Radium Institute Research Unit, Queensland Institute of Medical Research, Brisbane, 4006, Queensland, Australia

    Anthony L Cook & J Helen Leonard

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  1. Mireille Van Gele
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  2. Glen M Boyle
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Correspondence to Frank Speleman.

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Gele, M., Boyle, G., Cook, A. et al. Gene-expression profiling reveals distinct expression patterns for Classic versus Variant Merkel cell phenotypes and new classifier genes to distinguish Merkel cell from small-cell lung carcinoma. Oncogene 23, 2732–2742 (2004). https://doi.org/10.1038/sj.onc.1207421

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