McCannel Tara A, Burgess Barry L, Rao Nagesh P, Nelson Stanley F, Straatsma Bradley R
Department of Ophthalmology, David Geffen School of Medicine at UCLA, Jules Stein Eye Institute, Los Angeles, CA 90095-7000, USA.
Arch Ophthalmol. 2010 Sep;128(9):1170-7. doi: 10.1001/archophthalmol.2010.180.
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.
报告脉络膜黑色素瘤细针穿刺活检标本的综合分子分析，以鉴定候选肿瘤癌基因。
对31例脉络膜黑色素瘤细针穿刺活检标本进行分析，采用黑色素瘤的细胞病理学诊断、3号染色体荧光原位杂交、细胞遗传学特征分析（基因芯片人类250K NSPI图谱阵列；Affymetrix公司，加利福尼亚州圣克拉拉）以及基因表达谱分析（基因芯片人类基因组U133 Plus 2.0阵列，Affymetrix公司）。这些分析通过细胞遗传学异常聚类、按3号染色体缺失和6号染色体短臂增加进行分类，以及比较3号染色体缺失和6号染色体短臂增加肿瘤的基因表达谱，以根据细胞遗传学特征鉴定差异表达基因。
本研究纳入的31例脉络膜黑色素瘤活检标本中，19例肿瘤有3号染色体缺失，12例无3号染色体缺失的肿瘤有6号染色体短臂增加。对这两组进行的比较RNA分析显示，相对于6号染色体短臂增加的肿瘤，3号染色体缺失肿瘤中有49个基因表达高出4倍以上，31个基因表达低于4倍。
脉络膜黑色素瘤细针穿刺活检标本的分子分析显示出两组细胞遗传学上不同的群体特征，分别为3号染色体缺失或6号染色体短臂增加。相对于6号染色体短臂增加的黑色素瘤，3号染色体缺失的黑色素瘤综合RNA分析揭示了表达较高和较低的基因，并鉴定出一些先前研究中未报道的基因。
3号染色体缺失和6号染色体短臂增加的黑色素瘤之间差异表达的基因可能为脉络膜黑色素瘤的生物学特性提供新知识，并可能有助于靶向治疗的发展。
