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

• Published in: Oncogene Vol. 23; no. 15; pp. 2732 - 2742
• Main Authors: Gele, Mireille Van, Boyle, Glen M, Cook, Anthony L, Vandesompele, Jo, Boonefaes, Tom, Rottiers, Pieter, Roy, Nadine Van, De Paepe, Anne, Parsons, Peter G, Leonard, J Helen, Speleman, Frank
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.04.2004; Nature Publishing; Nature Publishing Group
• Subjects: Apoptosis; Arrays; Biological and medical sciences; Biomarkers, Tumor; Cancer; Carcinoma, Merkel Cell - genetics; Carcinoma, Small Cell - genetics; Cell Biology; Cell Line, Tumor; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cluster Analysis; Diagnosis, Differential; DNA microarrays; DNA, Complementary - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Genes; Genomics; Human Genetics; Humans; Internal Medicine; Lung cancer; Lung carcinoma; Lung Neoplasms - genetics; Medical research; Medical sciences; Medicine; Medicine & Public Health; Molecular and cellular biology; Oligonucleotide Array Sequence Analysis; oncogenomics; Oncology; Pathogenesis; Phenotype; Phenotypes; Pneumology; Reverse Transcriptase Polymerase Chain Reaction; Skin cancer; Skin Neoplasms - genetics; Therapeutic applications; Tumors; Tumors of the respiratory system and mediastinum; Queensland Australia; Belgium; Australia; Classic/Variant; differential diagnosis; small-cell lung carcinoma; Merkel cell carcinoma; differential expression profiling; Lung disease; Respiratory disease; Bonchopulmonary small cell carcinoma; Merkel cell; Lung cancer; Malignant tumor; Gene expression; Carcinogenesis; Differential diagnostic; Variant; Phenotype; Gene; Bronchus disease
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1207421

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.