INTRODUCTION Inherited mutations are easily detected factors that influence the disease courses and optimal treatment strategies of some cancers. Germline mutations in BRCA associated protein-1 (BAP1) are associated with unique disease profiles in mesothelioma, atypical spitz nevi, and uveal melanoma (UM), but the patient characteristics of an unselected population of BAP1 carriers identified by an ascertainment prevalence study are unknown. METHODS We collected blood samples, cancer histories, and occupational exposures from 183 unselected patients with BAP1-related diseases. Clinical information for each patient was obtained from medical records. Germline DNA was extracted from blood samples and sequenced using a next-generation sequencing assay. We tested screening criteria developed to identify patients with a possible germline BAP1 mutation. RESULTS Pathogenic or likely pathogenic germline BAP1 mutations were observed in 5 of 180 sequenced specimens and were exclusively found in patients identified by our screening criteria. Several patients with characteristics suspicious for a heritable deleterious mutation did not have a germline BAP1 mutation. The prevalence of pathogenic germline BAP1 mutations in patients with mesothelioma was 4.4% (95% confidence interval 1.1-11.1). CONCLUSIONS Results from the first unselected prevalence ascertainment study of germline BAP1 alterations suggest that the frequency of this mutation is low among patients with mesothelioma. The proposed screening criteria successfully identified all patients with germline BAP1-mutant mesothelioma. These screening guidelines may assist physicians in selecting patients that would benefit from genetic testing. Future efforts should validate and refine these criteria and search for other germline mutations associated with mesothelioma and related diseases.

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简要报告：识别种系 BAP1 突变载体的筛选标准的流行和初步验证

引言 遗传性突变是很容易检测到的因素，会影响某些癌症的病程和最佳治疗策略。BRCA 相关蛋白 1 (BAP1) 的种系突变与间皮瘤、非典型斯皮茨痣和葡萄膜黑色素瘤 (UM) 的独特疾病谱相关，但通过确定流行率研究确定的未选择的 BAP1 携带者群体的患者特征尚不清楚. 方法 我们收集了 183 名未选择的 BAP1 相关疾病患者的血液样本、癌症病史和职业暴露情况。每位患者的临床信息均从医疗记录中获得。从血液样本中提取生殖系 DNA 并使用下一代测序分析进行测序。我们测试了为识别可能存在种系 BAP1 突变的患者而制定的筛选标准。结果 在 180 个测序样本中的 5 个中观察到致病性或可能致病性种系 BAP1 突变，并且仅在我们的筛选标准确定的患者中发现。一些具有可疑遗传性有害突变特征的患者没有种系 BAP1 突变。间皮瘤患者中致病性种系 BAP1 突变的流行率为 4.4%（95% 置信区间 1.1-11.1）。结论 第一次未选择的生殖系 BAP1 改变流行率确定研究的结果表明，这种突变在间皮瘤患者中的频率较低。提议的筛选标准成功地鉴定了所有患有种系 BAP1 突变间皮瘤的患者。这些筛查指南可帮助医生选择可从基因检测中受益的患者。