葡萄膜黑色素瘤 (UM) 是一种罕见但具有侵袭性的眼癌，导致 50% 以上的转移死亡率。在芬兰和美国，家族性 UM 患者占 1%-6%，大多数缺乏确定的遗传原因，而 8% 的患者与其他癌症综合征有关。除了已经研究的 BAP1 和 MBD4 之外，我们还通过对 270 名连续入组的芬兰 UM 患者中与 UM、BAP1 或肾细胞癌相关的 19 个基因进行靶向扩增子测序，搜索了与 UM 易感性相关的新遗传关联。关键 UM 驱动程序 GNAQ、GNA11、CYSLTR2、PLCB4、EIF1AX 和 SF3B1 缺乏致病性种系变异。一名患者携带致病性 BRCA1 变异 c.3626del p.(Leu1209*)，一名患者携带一种新型截短 MET 变异 c.252C > G p.(Tyr84*)，被归类为可能致病。 FLCN 和 BRCA2 先前在 UM 患者中被鉴定为致病性变异，但在我们的队列中不存在此类变异。两名患者为致病性隐性 BLM 变异 c.2824-2A > T 杂合子。已识别变异的携带者均未患有家族性 UM。我们将 BRCA1 和 MET 确定为芬兰 UM 患者中具有致病性种系变异的基因，每个基因的频率均为 0.4%（95% 置信区间，0-2）。© 2024 作者。色素细胞

Uveal melanoma (UM) is a rare yet aggressive eye cancer causing over 50% mortality from metastasis. Familial UM, amounting to 1%-6% of patients in Finland and the United States, mostly lack identified genetic cause, while 8% show associations with other cancer syndromes. We searched novel genetic associations for predisposition to UM, additional to already studied BAP1 and MBD4, by using targeted amplicon sequencing of 19 genes associated with UM, BAP1, or renal cell carcinoma in 270 consecutively enrolled Finnish patients with UM. Key UM drivers GNAQ, GNA11, CYSLTR2, PLCB4, EIF1AX, and SF3B1 lacked pathogenic germline variants. One patient carried the pathogenic BRCA1 variant c.3626del p.(Leu1209*), and one harbored a novel truncating MET variant c.252C > G p.(Tyr84*), classified as likely pathogenic. FLCN and BRCA2, previously identified with pathogenic variants in patients with UM, did not have such variants in our cohort. Two patients were heterozygous for a pathogenic recessive BLM variant c.2824-2A > T. None of the carriers of identified variants had familial UM. We identified BRCA1 and MET as genes with pathogenic germline variants in Finnish UM patients, each with a frequency of 0.4% (95% confidence interval, 0-2).© 2024 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.