Singh A D, Wang M X, Donoso L A, Shields C L, De Potter P, Shields J A
Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Semin Oncol. 1996 Dec;23(6):768-72.
Uveal melanoma usually occurs sporadically in the absence of obvious genetic predisposing factors. However, in rare patients, there is a suggestion that there may be genetic predisposition. Rare occurrences of familial uveal melanoma are believed to be inherited in an autosomal dominant mode. There are a few clinical conditions that can predispose to or be associated with uveal melanoma, including ocular melanocytosis, neurofibromatosis type I, and familial atypical mole and melanoma syndrome. Nonrandom cytogenetic changes in uveal melanoma are characterized by monosomy 3, trisomy 8, and structural or numerical abnormalities of chromosome 6. Alterations of chromosome 9p are less frequently observed. CDKN2 gene, a cutaneous melanoma predisposition gene, is probably not a uveal melanoma predisposition gene as evidenced by the lack of somatic mutations involving this gene in uveal melanoma samples and the absence of germline mutations in familial uveal melanoma patients. Transgenic mouse models developed using a tyrosinase promoter tagged with a mutated ras gene or SV40-Tag oncoprotein develop retinal pigment epithelium tumors that resemble uveal melanoma. We propose that uveal melanoma cases be categorized on genetic basis according to a new classification system. This classification scheme will help to identify and uniformly categorize uveal melanoma patients with genetic predisposition. Such patients offer unique opportunities for studying the genetic aspects of uveal melanoma and, therefore, appropriate tissue samples should be obtained from them for molecular genetic studies. Further studies are needed to fully understand the genetic aspects of uveal melanoma.
葡萄膜黑色素瘤通常在没有明显遗传易感性因素的情况下散发性发生。然而，在少数患者中，提示可能存在遗传易感性。家族性葡萄膜黑色素瘤的罕见病例被认为是以常染色体显性模式遗传的。有一些临床情况可诱发葡萄膜黑色素瘤或与之相关，包括眼部黑变病、I型神经纤维瘤病以及家族性非典型痣和黑色素瘤综合征。葡萄膜黑色素瘤的非随机细胞遗传学改变以3号染色体单体、8号染色体三体以及6号染色体的结构或数目异常为特征。9号染色体短臂的改变较少见。CDKN2基因是一种皮肤黑色素瘤易感基因，可能不是葡萄膜黑色素瘤易感基因，这一点可由葡萄膜黑色素瘤样本中缺乏涉及该基因的体细胞突变以及家族性葡萄膜黑色素瘤患者中缺乏种系突变得到证明。使用带有突变ras基因或SV40-Tag癌蛋白的酪氨酸酶启动子构建的转基因小鼠模型会发生类似于葡萄膜黑色素瘤的视网膜色素上皮肿瘤。我们建议根据一种新的分类系统在遗传基础上对葡萄膜黑色素瘤病例进行分类。这种分类方案将有助于识别有遗传易感性的葡萄膜黑色素瘤患者并对其进行统一分类。这类患者为研究葡萄膜黑色素瘤的遗传方面提供了独特机会，因此，应该从他们身上获取合适的组织样本进行分子遗传学研究。需要进一步研究以全面了解葡萄膜黑色素瘤的遗传方面。
