Identification of Candidate Tumor Oncogenes by Integrative Molecular Analysis of Choroidal Melanoma Fine-Needle Aspiration Biopsy Specimens

Objective: To report integrative molecular analysis of choroidal melanoma fine-needle aspiration biopsy specimens to identify candidate tumor oncogenes. Methods: Thirty-one choroidal melanoma fine-needle aspiration biopsy specimens were analyzed using cytopathologic diagnosis of melanoma, fluorescence in situ hybridization for chromosome 3, cytogenetic characterization (Gene Chip Human 250K NSPI Mapping Arrays; Affymetrix, Santa Clara, California), and gene expression profiles (Gene Chip Human Genome U133 Plus 2.0 Arrays, Affymetrix). These analyses were performed by clustering of cytogenetic aberrations, sorting by chromosome 3 loss and chromosome 6p gain, and comparing gene expression profiles in chromosome 3 loss and chromosome 6p gain tumors to identify genes with differential expression based on cytogenetic characteristics. Results: Of 31 choroidal melanoma biopsy specimens included in this study, 19 tumors had chromosome 3 loss, and 12 tumors without chromosome 3 loss had chromosome 6p gain. Comparative RNA analysis for these 2 groups revealed 49 genes with greater than 4-fold higher expression and 31 genes with greater than 4-fold lower expression in chromosome 3 loss tumors relative to chromosome 6p gain tumors. Conclusions: Molecular analysis of choroidal melanoma fine-needle aspiration biopsy specimens demonstrated 2 cytogenetically distinct groups characterized by chromosome 3 loss or chromosome 6p gain. In chromosome 3 loss melanomas relative to chromosome 6p gain melanomas, integrative RNA analysis revealed genes with higher expression and lower expression and identified several genes that have not been reported in previous studies. Clinical Relevance: Genes differentially expressed between chromosome 3 loss and chromosome 6p gain melanomas may provide new knowledge about the biologic nature of choroidal melanoma and may contribute to the development of targeted therapies.