癌症基因组分析 (CGP) 偶尔会将癌症易感基因 (CSG) 中的致病性种系变异 (PGV) 识别为次要发现。在这里，我们根据日本 CGP 测试的全国真实数据分析了 PGV 的患病率和临床特征。我们使用综合国家数据库分析了 23,928 名实体癌患者的基因组信息和临床特征，这些患者在 2019 年 6 月至 2021 年 12 月期间接受了纯肿瘤 (n = 20,189) 或配对肿瘤-正常 (n = 3,739) 测序 CGP 测试。我们为所有变异赋予了临床意义，并强调了 PGV 的患病率和特征。我们对肿瘤正常测序队列的初步分析显示，152 名患者 (4.1%) 在 15 个 CSG 中携带 PGV。在 783 个种系变异中，113 个被注释为 PGV，70 个被注释为良性变异，600 个被注释为意义不确定的变异。鉴定出的 PGV 数量在 BRCA1/2 中最高，有 56 个，其次是 TP53，有 18 个。PGV 在卵巢癌和腹膜癌中最常见，包括亚洲常见的癌症类型。在仅肿瘤测序队列中，根据欧洲肿瘤内科学会针对种系肿瘤分析的建议，在 26 个 CSG 的 5,184 个致病性体细胞变异中提取了 784 个（15.1%）。PGV 的患病率与之前相似欧洲和美国均有报道。这是亚洲基于真实肿瘤正常测序测试的最大分析。肿瘤正常测序 CGP 测试的更广泛使用对于评估 PGV 可能是合理的。

Cancer genome profiling (CGP) occasionally identifies pathogenic germline variants (PGVs) in cancer susceptibility genes (CSGs) as secondary findings. Here, we analyzed the prevalence and clinical characteristics of PGVs based on nationwide real-world data from CGP tests in Japan. We analyzed the genomic information and clinical characteristics of 23,928 patients with solid cancers who underwent either tumor-only (n = 20,189) or paired tumor-normal (n = 3,739) sequencing CGP tests between June 2019 and December 2021 using the comprehensive national database. We assigned clinical significance for all variants and highlighted the prevalence and characteristics of PGVs. Our primary analysis of the tumor-normal sequencing cohort revealed that 152 patients (4.1%) harbored PGVs in 15 CSGs. Among 783 germline variants, 113 were annotated as PGVs, 70 as benign variants, and 600 as variants of uncertain significance. The number of PGVs identified was highest in BRCA1/2, with 56, followed by TP53, with 18. PGVs were the most prevalent in ovarian and peritoneal cancers, including among cancer types common in Asia. In the tumor-only sequencing cohort, of the 5,184 pathogenic somatic variants across 26 CSGs, 784 (15.1%) were extracted according to the European Society for Medical Oncology recommendations for germline-focused tumor analysis.The prevalence of PGVs was similar to that previously reported in Europe and the United States. This is the largest analysis based on real-world tumor-normal sequencing tests in Asia. The more widespread use of the tumor-normal sequencing CGP test could be reasonable for evaluating PGVs.