High-throughput sequencing has greatly contributed to precision medicine. However, challenges remain in reporting secondary findings (SFs) of germline pathogenic variants and managing the affected patients. The aim of this study was to examine the incidence of SFs in Japanese cancer patients using whole exome sequencing (WES) and to understand patient preferences regarding SF disclosure. WES was conducted for 2480 cancer patients. Genomic data were screened and classified for variants of 59 genes listed by the American College of Medical Genetics and Genomics SF v2.0 and for an additional 13 hereditary cancer-related genes. Majority of the participants (68.9%; 1709/2480) opted for disclosure of their SFs. Thirty-two pathogenic or likely pathogenic variants, including BRCA1 (7 patients), BRCA2 (4), CHEK2 (4), PTEN (3), MLH1 (3), SDHB (2), MSH6 (1), NF1 (1), EXT2 (1), NF1 (1), NTRK1 (1), MYH7 (3), MYL2 (1), TNNT2 (1), LDLR (2), FBN1 (1), and KCNH2 (1) were recognized in 36 patients (1.5%). Twenty-eight (77.8%) patients underwent genetic counseling and received their SF results. Eighteen (64.3%) patients underwent clinical management for SFs. Genetic validation tests were administered significantly more frequently to patients with than without a SF-related personal history (P = 0.025). This was a first attempt at a large-scale systematic exome analysis in Japan; nevertheless, many cancer patients opted for disclosure of SFs and accepted or considered clinical management.

高通量测序极大地促进了精密医学的发展。但是，在报告种系致病变异的次要发现（SF）和管理受影响的患者方面仍然存在挑战。这项研究的目的是使用全外显子组测序（WES）检查日本癌症患者中SF的发生率，并了解患者对SF披露的偏好。对2480名癌症患者进行了WES。对基因组数据进行筛选，并对美国医学遗传学和基因组学SF v2.0列出的59个基因的变体进行分类，并对13个与遗传性癌症相关的基因进行分类。多数参与者（68.9％； 1709/2480）选择披露自己的财务报告。32种病原体或可能的病原体变体，包括BRCA1（7例），BRCA2（4），CHEK2（4），PTEN（3），MLH1（3），SDHB（2），MSH6（1），NF1（1），EXT2（1），NF1（1），NTRK1（1），MYH7（36）（3％）（36）（1.5％）认识到（3），MYL2（1），TNNT2（1），LDLR（2），FBN1（1）和KCNH2（1）。28名（77.8％）患者接受了遗传咨询并获得了SF结果。十八名（64.3％）患者接受了SF的临床治疗。与没有SF相关个人病史的患者相比，对基因验证试验的频率明显更高（P  = 0.025）。这是在日本进行大规模系统外显子组分析的首次尝试；但是，许多癌症患者选择披露SF并接受或考虑了临床治疗。