Abstract
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.
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This study was supported by JSPS KAKENHI (grant number JP17K08942) and AMED (grant number 15kk0105001h0102). English Language editing services supplied by Eigo Eibun Tensaku Center.
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439_2020_2207_MOESM3_ESM.jpg
Fig. S1 Workflow for the study performed by Project HOPE. Consent forms from patients who agreed to participate in the study were entered into their electronic medical records and then stored in the Medical Information Management Office. Blood samples were collected in the operating room. Fresh cancerous and non-cancerous tissues were collected by a pathologist from the surgically resected material. After anonymization in the Personal Information Management Office, these samples were delivered to the laboratory. Over 200 staff members were involved in the study, including those conducting the laboratory analysis)
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Horiuchi, Y., Matsubayashi, H., Kiyozumi, Y. et al. Disclosure of secondary findings in exome sequencing of 2480 Japanese cancer patients. Hum Genet 140, 321–331 (2021). https://doi.org/10.1007/s00439-020-02207-6
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DOI: https://doi.org/10.1007/s00439-020-02207-6