Martorano Lisa M, Winkelmann Richard R, Cebulla Colleen M, Abdel-Rahman Mohamed H, Campbell Shannon M
Richmond Medical Center, University Hospitals, Cleveland, OH, USA.
Int J Dermatol. 2014 Jun;53(6):657-63. doi: 10.1111/ijd.12386. Epub 2014 Apr 2.
Ocular melanoma is a rare subtype of melanoma, which includes uveal melanoma (UM) and conjunctival melanoma. UM is associated with an increased risk of cutaneous melanoma (CM) in addition to mesothelioma, skin lesions such as epithelioid atypical Spitz tumors, and other internal malignancies due to a germline mutation of the BRCA1-associated protein 1 (BAP1) gene. Such familial risks are important for dermatologists to recognize when screening patients with a history of UM for CM and other malignancies. Molecular genetics further help to elucidate the connections between UM and CM by revealing similarities and differences in important mutations among the melanoma subtypes. Both UM and CM have been shown to harbor germline mutation of BAP1. However, somatic mutations in either GNAQ or GNA11 are unique to UM tumors and could be used as potential markers to differentiate UM from metastatic CM and act as direct therapeutic targets. However, CM-associated BRAF and CDKN2A mutations are rare in UM. This review addresses the clinical features, pathogenesis, and current treatment options of UM, focusing on UM and the BAP1 cancer syndrome to raise awareness of ocular melanoma and its greater role in the predisposition to a hereditary cancer syndrome.
眼黑色素瘤是黑色素瘤的一种罕见亚型，包括葡萄膜黑色素瘤（UM）和结膜黑色素瘤。除间皮瘤、上皮样非典型斯皮茨瘤等皮肤病变以及由于BRCA1相关蛋白1（BAP1）基因种系突变导致的其他内部恶性肿瘤外，UM还与皮肤黑色素瘤（CM）风险增加相关。在对有UM病史的患者进行CM和其他恶性肿瘤筛查时，这种家族性风险对皮肤科医生来说很重要，需要加以识别。分子遗传学通过揭示黑色素瘤亚型中重要突变的异同，进一步有助于阐明UM和CM之间的联系。已证明UM和CM都存在BAP1种系突变。然而，GNAQ或GNA11中的体细胞突变是UM肿瘤所特有的，可作为区分UM与转移性CM的潜在标志物，并作为直接治疗靶点。然而，CM相关的BRAF和CDKN2A突变在UM中很少见。本综述阐述了UM的临床特征、发病机制和当前的治疗选择，重点关注UM和BAP1癌症综合征，以提高对眼黑色素瘤及其在遗传性癌症综合征易感性中更大作用的认识。
