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Arch Ophthalmol. 2010 Sep;128(9):1170-7. doi: 10.1001/archophthalmol.2010.180.

Identification of candidate tumor oncogenes by integrative molecular analysis of choroidal melanoma fine-needle aspiration biopsy specimens.

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Department of Ophthalmology, David Geffen School of Medicine at UCLA, Jules Stein Eye Institute, Los Angeles, CA 90095-7000, USA.



To report integrative molecular analysis of choroidal melanoma fine-needle aspiration biopsy specimens to identify candidate tumor oncogenes.


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 (GeneChip Human 250K NSPI Mapping Arrays; Affymetrix, Santa Clara, California), and gene expression profiles (GeneChip 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.


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.


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.


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.

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