Department of Dermatology, Medical University of Graz, Graz, Austria.
Nat Genet. 2011 Aug 28;43(10):1018-21. doi: 10.1038/ng.910.
Common acquired melanocytic nevi are benign neoplasms that are composed of small, uniform melanocytes and are typically present as flat or slightly elevated pigmented lesions on the skin. We describe two families with a new autosomal dominant syndrome characterized by multiple, skin-colored, elevated melanocytic tumors. In contrast to common acquired nevi, the melanocytic neoplasms in affected family members ranged histopathologically from epithelioid nevi to atypical melanocytic proliferations that showed overlapping features with melanoma. Some affected individuals developed uveal or cutaneous melanomas. Segregating with this phenotype, we found inactivating germline mutations of BAP1, which encodes a ubiquitin carboxy-terminal hydrolase. The majority of melanocytic neoplasms lost the remaining wild-type allele of BAP1 by various somatic alterations. In addition, we found BAP1 mutations in a subset of sporadic melanocytic neoplasms showing histological similarities to the familial tumors. These findings suggest that loss of BAP1 is associated with a clinically and morphologically distinct type of melanocytic neoplasm.
常见的获得性黑色素痣是良性肿瘤，由小而均匀的黑色素细胞组成，通常表现为扁平或略微隆起的色素性皮损。我们描述了两个具有新常染色体显性遗传综合征的家族，其特征为多发性、肤色、隆起的黑色素细胞瘤。与常见的获得性痣不同，受影响家族成员的黑色素细胞瘤在组织病理学上从上皮样痣到具有与黑色素瘤重叠特征的非典型黑色素细胞增生不等。一些受影响的个体发生葡萄膜或皮肤黑色素瘤。与这种表型共分离，我们发现编码泛素羧基末端水解酶的 BAP1 种系失活突变。大多数黑色素细胞瘤通过各种体细胞改变丢失了剩余的野生型 BAP1 等位基因。此外，我们还发现一组散发性黑色素细胞瘤存在 BAP1 突变，其组织学与家族性肿瘤相似。这些发现表明 BAP1 的缺失与临床上和形态学上明显不同类型的黑色素细胞瘤有关。
