Vivet-Noguer Raquel, Tarin Malcy, Roman-Roman Sergio, Alsafadi Samar
Uveal Melanoma Translational Group, Department of Translational Research, Institut Curie, PSL Research University, 75248 Paris, France.
Cancers (Basel). 2019 Jul 20;11(7):1019. doi: 10.3390/cancers11071019.
Uveal Melanoma (UM) is a rare and malignant intraocular tumor with dismal prognosis. Despite the efficient control of the primary tumor by radiation or surgery, up to 50% of patients subsequently develop metastasis, mainly in the liver. Once the tumor has spread from the eye, the treatment is challenging and the median survival is only nine months. UM represents an intriguing model of oncogenesis that is characterized by a relatively homogeneous histopathological architecture and a low burden of genetic alterations, in contrast to other melanomas. UM is driven by recurrent activating mutations in Gαq pathway, which are associated with a second mutation in BRCA1 associated protein 1 (), splicing factor 3b subunit 1 (), or eukaryotic translation initiation factor 1A X-linked (), occurring in an almost mutually exclusive manner. The monosomy of chromosome 3 is also a recurrent feature that is associated with high metastatic risk. These events driving UM oncogenesis have been thoroughly investigated over the last decade. However, no efficient related therapeutic strategies are yet available and the metastatic disease remains mostly incurable. Here, we review current knowledge regarding the molecular biology and the genetics of uveal melanoma and highlight the related therapeutic applications and perspectives.
葡萄膜黑色素瘤（UM）是一种罕见的恶性眼内肿瘤，预后不佳。尽管通过放疗或手术可有效控制原发性肿瘤，但仍有高达50%的患者随后会发生转移，主要转移至肝脏。一旦肿瘤从眼部扩散，治疗极具挑战性，中位生存期仅为9个月。与其他黑色素瘤不同，UM是一种有趣的肿瘤发生模型，其特征在于组织病理学结构相对均匀且基因改变负担较低。UM由Gαq途径中的复发性激活突变驱动，这些突变与BRCA1相关蛋白1、剪接因子3b亚基1或真核翻译起始因子1A X连锁的第二个突变几乎以互斥的方式发生。3号染色体单体也是一个反复出现的特征，与高转移风险相关。在过去十年中，这些驱动UM肿瘤发生的事件已得到深入研究。然而，目前尚无有效的相关治疗策略，转移性疾病大多仍无法治愈。在此，我们综述了关于葡萄膜黑色素瘤分子生物学和遗传学的当前知识，并强调了相关的治疗应用和前景。
