Discrimination between gene expression patterns in the invasive margin and the tumour core of malignant melanomas.
Genes that determine the invasive capacity of the invasive front of malignant melanomas (MM) have not yet been systematically investigated in vivo. Therefore, we combined laser pressure catapulting (LPC) microdissection with cDNA microarray technology (DermArray, Research Genetics, representing about 5700 genes) to systematically analyse differences in gene expression profiles between the invasive margin and the tumour centre in nine cases of vertical growth phase MM. Signal-to-noise statistical algorithms combined with hierarchical clustering were performed to determine class-separating genes. The gene encoding phosphoenolpyruvate carboxykinase 1 (PEPCK), the Homo sapiens gene similar to Saccharomyces cerevisiae SSM4 (TEB4), the gene encoding ribosomal protein L19, the Homo sapiens gene similar to the Aspergillus nidulans SudD (a suppressor of the bimD6 homologue), the gene encoding the interleukin-3 receptor alpha subunit, the gene encoding the inositol 1,4,5-triphosphate 3-kinase isoenzyme, and three anonymous expressed sequence tags were identified as class-separating genes. These genes significantly discriminate between the invasive front and the tumour centre. Using this set of genes, 15 out of 18 LPC-dissected MM regions could be grouped correctly. We conclude that the candidate genes identified could spark further research on MM progression and may provide novel prognostic parameters.
D000465:Algorithms; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D005656:Fungal Proteins / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053650:Interleukin-3 Receptor alpha Subunit; D007834:Lasers; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis; D011379:Prognosis; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D016185:Receptors, Interleukin-3 / Q000096:biosynthesis; D015854:Up-Regulation
D018076:DNA, Complementary; D005656:Fungal Proteins; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit; D020033:Protein Isoforms; D016185:Receptors, Interleukin-3; C112953:SUDD protein, Emericella nidulans; D017853:Phosphotransferases (Alcohol Group Acceptor); C069767:phosphoenolpyruvate carboxylase kinase; C051038:Inositol 1,4,5-trisphosphate 3-kinase; D017346:Protein Serine-Threonine Kinases