Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death
Gene expression profiling in uveal melanoma reveals two molecular classes and predicts metastatic death
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DOI：
10.1158/0008-5472.can-04-1750
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发表时间：
2004-10-15
期刊：
影响因子：
11.2
通讯作者：
Harbour, JW
中科院分区：
文献类型：
--
作者：
Onken, MD;Worley, LA;Harbour, JW
黑色素瘤是出了名的难以分类，因为缺乏独立的临床和病理分期。在这里，我们发现原发性葡萄膜黑色素瘤基于基因表达谱令人惊讶地分为两个不同的分子类。区分1类（低等级）和2类（高等级）的基因包括3号染色体上高度显著的下调基因簇和8q染色体上高度显著的上调基因簇，这与以往的细胞遗传学研究一致。三基因标记允许活检大小的肿瘤样本使用阵列或PCR平台准确地分配到肿瘤类别。最重要的是，这种分子分类强烈预测转移性死亡，优于其他临床和病理预后指标。这些研究为黑色素瘤的发病机制提供了新的见解，并为有效的临床预测测试提供了实践基础。
Melanomas are notoriously difficult to classify because of a lack of discrete clinical and pathological stages. Here, we show that primary uveal melanomas surprisingly cluster into two distinct molecular classes based on gene expression profile. Genes that discriminate class 1 (low-grade) from class 2 (high-grade) include highly significant clusters of down-regulated genes on chromosome 3 and up-regulated genes on chromosome 8q, which is consistent with previous cytogenetic studies. A three-gene signature allows biopsy-size tumor samples to be assigned accurately to tumor classes using either array or PCR platforms. Most importantly, this molecular classification strongly predicts metastatic death and outperforms other clinical and pathological prognostic indicators. These studies offer new insights into melanoma pathogenesis, and they provide a practical foundation for effective clinical predictive testing.