Analysis of N-ras Mutations in Human Cutaneous Melanoma: Tumor Heterogeneity Detected by Polymerase Chain Reaction/Single-Stranded Conformation Polymorphism Analysis

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Abstract
Determination of the activation state of oncogenes as well as tumor suppressor genes is a main subject of interest in the analysis of the mechanism of tumor initiation. In human melanoma, the c-myc and N-ras oncogenes have been found to be activated in approximately 50% and 15% of the analyzed material, respectively. These studies have mostly been done on fresh tumor material or cell lines. Only in a few cases has an attempt been made to look at tumor heterogeneity or clonality with respect to the activation of oncogenes. We have adjusted the polymerase chain reaction (PCR)/ single-stranded conformation polymorphism analysis (SSCP) technique to screen paraffin-embedded melanoma material for the presence of N-ras mutations and found genetic defects at particular progression stages. In one melanoma of the skin, we were able to sublocalize an N-ras mutation in the intraepidermal tumor part, that was absent in the part deeply invading the dermal layer. We conclude that a thorough investigation of N-ras activation in human melanoma should include analysis of histologically different parts of the tumor.