cDNA-array profiling of melanomas and paired melanocyte cultures

✍ Scribed by Carlo Mischiati; Pier Giorgio Natali; Alessia Sereni; Leonardo Sibilio; Ezio Giorda; Sandra Cappellacci; Maria Rita Nicotra; Giustino Mariani; Franco Di Filippo; Caterina Catricalà; Roberto Gambari; Paola Grammatico; Patrizio Giacomini

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 424 KB
• Volume: 207
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.20610

✦ Synopsis

Abstract

Three paired (from the same donor) sets of melanoma cells and normal melanocytes, established as early‐passage cultures from metastatic lesions and the uninvolved skin of three patients, were comparatively cDNA profiled by macroarrays (approximately 1,200 genes) and reverse transcription (RT)‐PCR. While 145 gene products were significantly (at least twofold) upregulated or downregulated in at least 1 pair, and 23 were in at least 2 pairs, only 3 (the signal transducer and activator of transcription STAT2, collagen type VI, and CD9) were concordantly modulated (downregulation) in all 3 pairs. Array results were validated by RT‐PCR on a small panel of surgically removed nevocellular nevi and metastatic melanoma lesions, and by immunohistochemistry on a large panel of benign and malignant lesions of the nevomelanocytic lineage. The three gene products were downregulated at different stages of melanoma progression. STAT2 was detectable in nevi (5/5) and most primary melanomas (11/12), but was lost in 10/15 metastatic lesions. Collagen type VI was expressed in nevi (5/5) and primary melanomas below a Breslow thickness of 1 mm (3/3), but was lost in 24/24 primary melanomas above this threshold, and in metastatic melanomas (10/10). The tetraspanin CD9 molecule was expressed in 18/18 nevi, but was lost in 20/28 primary melanomas (including thin lesions), and in 24/52 metastatic lesions. These data provide the proof of principle that cDNA profiling of paired melanocyte/melanoma cultures sorts out novel, early signatures of melanocyte transformation that could contribute to the clinical management of patients at high risk of metastatic disease. J. Cell. Physiol. © 2006 Wiley‐Liss, Inc.