Abstract：
UNASSIGNED: BAP1-inactivated melanocytic tumors represent a subset of epithelioid melanocytic neoplasms resulting from biallelic inactivation of the BAP1 gene and by a driver mutation that activate the MAP kinase pathway, most commonly BRAFV600E. They occur sporadically or, less common, in the setting of BAP1 tumor predisposition syndrome caused by a BAP1 germline mutation that predisposes to several malignancies including cutaneous and uveal melanoma. To date, only few cases of BAP1-inactivated melanomas have been reported. We present a case of a 35-year-old woman presented with a melanocytic lesion microscopically composed of 3 distinct melanocytic populations, suggesting a stepwise progression model to melanoma from a conventional nevus through a melanocytoma stage. This progression was also supported from a molecular viewpoint given BRAFV600E, BAP1, and TERT-p hot spot mutations detected by targeted mutational analysis. Four atypical melanocytic lesions were removed from the patient\'s back, and the same A BAP1 c.856A>T, p.(Lys286Ter) mutation was detected on either tumoral or normal tissue samples. To the best of our knowledge, this is the first case of BAP1-inactivated melanoma with a documented TERT-p hot spot mutation manifesting as the first presentation of BAP1 tumor predisposition syndrome.
摘要：
未经证实：BAP1灭活的黑素细胞肿瘤代表由BAP1基因双等位基因失活和激活MAP激酶途径的驱动突变引起的上皮样黑素细胞肿瘤的一个子集，最常见的BRAFV600E。它们偶尔发生，或者，不太常见，在由BAP1种系突变引起的BAP1肿瘤易感综合征的背景下，该突变易感多种恶性肿瘤，包括皮肤和葡萄膜黑色素瘤。迄今为止,仅报道了少数BAP1灭活的黑色素瘤病例。我们介绍了一例35岁的女性，在显微镜下表现为由3种不同的黑素细胞群组成的黑素细胞病变，提示从传统痣到黑色素细胞瘤阶段的黑色素瘤逐步进展模型。从BRAFV600E的分子观点来看，这一进展也得到了支持，通过靶向突变分析检测到BAP1和TERT-p热点突变。从病人背部切除了4个不典型的黑色素细胞损伤,和相同的BAP1c.856A>T，在肿瘤或正常组织样品上检测到p.(Lys286Ter)突变。据我们所知,这是首例BAP1灭活的黑色素瘤,其TERT-p热点突变被证实是BAP1肿瘤易感综合征的首例.
