Department of Ophthalmology, Erasmus University Medical Centre, Rotterdam, The Netherlands; Department of Clinical Genetics, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Department of Pathology, Erasmus University Medical Centre, Rotterdam, The Netherlands.
Ophthalmology. 2016 May;123(5):1118-28. doi: 10.1016/j.ophtha.2016.01.023. Epub 2016 Feb 26.
To investigate the prevalence and prognostic value of SF3B1 and EIF1AX mutations in uveal melanoma (UM) patients.
Case series.
Cohort of 151 patients diagnosed with and treated for UM.
SF3B1 and EIF1AX mutations in primary tumors were investigated using whole-exome sequencing (n = 25) and Sanger sequencing (n = 151). For the detection of BAP1 mutations, a previously reported cohort of 90 patients was extended using BAP1 sequencing or immunohistochemistry.
The status of SF3B1, EIF1AX, and BAP1 in tumors of patients were correlated to clinical, histopathologic, and genetic parameters. Survival analyses were performed for patients whose tumors had SF3B1, EIF1AX, and BAP1 mutations.
Patients with tumors harboring EIF1AX mutations rarely demonstrated metastases (2 of 28 patients) and overall had a longer disease-free survival (DFS; 190.1 vs. 100.2 months; P < 0.001). Within the patient group with disomy 3, UM patients with an SF3B1 mutation had an increased metastatic risk compared with those without an SF3B1 mutation (DFS, 132.8 vs. 174.4 months; P = 0.008). Patients with such a mutation were more prone to demonstrate late metastases (median, 8.2 years; range, 23-145 months). Patients with UM and loss of BAP1 expression had a significantly decreased survival (DFS, 69.0 vs. 147.9 months; P < 0.001).
According to our data, patients with UM can be classified into 3 groups, of which EIF1AX-mutated tumors and tumors without BAP1, SF3B1, or EIF1AX mutations are associated with prolonged survival and low metastatic risk, SF3B1-mutated tumors are associated with late metastasis, and tumors with an aberrant BAP1 are associated with an early metastatic risk and rapid decline in patient DFS.
研究 SF3B1 和 EIF1AX 突变在葡萄膜黑色素瘤（UM）患者中的发生率和预后价值。
病例系列。
151 例经诊断和治疗的 UM 患者的队列。
使用全外显子组测序（n=25）和 Sanger 测序（n=151）检测原发肿瘤中的 SF3B1 和 EIF1AX 突变。为了检测 BAP1 突变，扩展了之前报道的 90 例患者队列，使用 BAP1 测序或免疫组织化学进行检测。
患者肿瘤中 SF3B1、EIF1AX 和 BAP1 的状态与临床、组织病理学和遗传参数相关。对肿瘤存在 SF3B1、EIF1AX 和 BAP1 突变的患者进行生存分析。
携带 EIF1AX 突变的患者很少发生转移（28 例患者中有 2 例），无疾病进展生存期（DFS）更长（190.1 与 100.2 个月；P<0.001）。在三体 3 的患者组中，与无 SF3B1 突变的患者相比，SF3B1 突变的 UM 患者转移风险增加（DFS，132.8 与 174.4 个月；P=0.008）。携带这种突变的患者更易发生晚期转移（中位时间为 8.2 年；范围为 23-145 个月）。BAP1 表达缺失的 UM 患者生存明显降低（DFS，69.0 与 147.9 个月；P<0.001）。
根据我们的数据，UM 患者可分为 3 组，其中 EIF1AX 突变肿瘤和无 BAP1、SF3B1 或 EIF1AX 突变的肿瘤与生存时间延长和低转移风险相关，SF3B1 突变肿瘤与晚期转移相关，而存在异常 BAP1 的肿瘤与早期转移风险和患者 DFS 迅速下降相关。
