Emerging insights into the molecular pathogenesis of uveal melanoma.
Emerging insights into the molecular pathogenesis of uveal melanoma.
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DOI：
10.2217/14796694.4.5.629
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Harbour JW
中科院分区：
文献类型：
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作者：
Landreville S;Agapova OA;Harbour JW
葡萄膜黑色素瘤是最常见的眼部原发性癌症，通常不仅导致视力丧失，而且导致多达一半的患者转移性死亡。多年来，葡萄膜黑色素瘤的分子发病机制的细节仍然难以捉摸。然而，在过去的十年中，许多这些细节已经出现，揭示了原发性肿瘤如何演变和发展的迷人而复杂的故事。破坏细胞周期和凋亡控制的早期事件导致葡萄膜黑素细胞的恶性转化和增殖。随后，生长中的肿瘤遇到一个关键的分叉点，在那里它沿着两条遗传途径之一进展，这两条遗传途径具有非常不同的遗传特征（单体3与6p获得）和转移倾向。晚期遗传事件的特征是非整倍体增加，其中大部分是非特异性的。然而，特定的染色体改变，如染色体8p的丢失，可以加速易感肿瘤转移的发生。两者合计，该发病机制方案可用于构建葡萄膜黑色素瘤的分子基础和病理学相关分类，其可用于临床个性化患者管理。
Uveal melanoma is the most common primary cancer of the eye, and often results not only in vision loss, but also in metastatic death in up to half of patients. For many years, the details of the molecular pathogenesis of uveal melanoma remained elusive. In the past decade, however, many of these details have emerged to reveal a fascinating and complex story of how the primary tumor evolves and progresses. Early events that disrupt cell cycle and apoptotic control lead to malignant transformation and proliferation of uveal melanocytes. Later, the growing tumor encounters a critical bifurcation point, where it progresses along one of two genetic pathways with very distinct genetic signatures (monosomy 3 vs 6p gain) and metastatic propensity. Late genetic events are characterized by increasing aneuploidy, most of which is nonspecific. However, specific chromosomal alterations, such as loss of chromosome 8p, can hasten the onset of metastasis in susceptible tumors. Taken together, this pathogenetic scheme can be used to construct a molecularly based and prognostically relevant classification of uveal melanomas that can be used clinically for personalized patient management.