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cDNA‐array profiling of melanomas and paired melanocyte cultures
Author(s) -
Mischiati Carlo,
Natali Pier Giorgio,
Sereni Alessia,
Sibilio Leonardo,
Giorda Ezio,
Cappellacci Sandra,
Nicotra Maria Rita,
Mariani Giustino,
Di Filippo Franco,
Catricalà Caterina,
Gambari Roberto,
Grammatico Paola,
Giacomini Patrizio
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20610
Subject(s) - melanoma , melanocyte , stat2 , complementary dna , breslow thickness , immunohistochemistry , gene expression profiling , biology , pathology , downregulation and upregulation , cancer research , metastasis , medicine , gene expression , gene , cancer , stat protein , stat3 , genetics , sentinel lymph node , breast cancer
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.