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In Japan, a limited number of laboratories perform comprehensive genetic testing for rare diseases; this study investigated the attitudes of these laboratories toward the disclosure of secondary finding (SF). Following a preliminary survey, we identified laboratories conducting comprehensive genetic testing for participation. Subsequently, an online survey involving 20 selected facilities was conducted. The response rate was 80% (16/20). Of the 14 facilities, 71.4% had SFs. While 42.9% of them had a policy to disclose SFs with clinical utility, only 14.3% actively searched for actionable variants that could be included in the American College of Medical Genetics and Genomics list. Japan was less enthusiastic than the USA regarding SF disclosure. With regard to the reasons for not disclosing SFs, the factors "the thought that participants may have a low desire for SFs" and "uncertainty regarding their wish" were considered more important than in the USA. A content analysis of what was sought as a solution to this difficulty revealed a need to improve databases on pathogenicity and actionability and collect public thoughts on the issue. The factor "to promote entry in research" was not considered a critical reason for disclosing SFs, indicating that the thirst for information was not possibly due to anxiety but rather due to scientific interest. Japanese medical professionals may not be confident that society requires the disclosure of SFs. To improve the environment, it is necessary to survey the public regarding their thoughts on SF disclosure and discuss this issue in society. [ABSTRACT FROM AUTHOR]

Background: Heterogeneous genetic loci contribute to hereditary hearing loss; more than 100 deafness genes have been identified, and the number is increasing. To detect pathogenic variants in multiple deafness genes, in addition to novel candidate genes associated with hearing loss, whole exome sequencing (WES), followed by analysis prioritizing genes categorized in four tiers, were applied.Results: Trios from families with non-syndromic or syndromic hearing loss (n = 72) were subjected to WES. After segregation analysis and interpretation according to American College of Medical Genetics and Genomics guidelines, candidate pathogenic variants in 11 previously reported deafness genes (STRC, MYO15A, CDH23, PDZD7, PTPN11, SOX10, EYA1, MYO6, OTOF, OTOG, and ZNF335) were identified in 21 families. Discrepancy between pedigree inheritance and genetic inheritance was present in one family. In addition, eight genes (SLC12A2, BAIAP2L2, HKDC1, SVEP1, CACNG1, GTPBP4, PCNX2, and TBC1D8) were screened as single candidate genes in 10 families.Conclusions: Our findings demonstrate that four-tier assessment of WES data is efficient and can detect novel candidate genes associated with hearing loss, in addition to pathogenic variants of known deafness genes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Because of the rapid development in genomics, more research findings have emerged. However, the association between society and research results remains controversial. This article examines the experiences and attitudes of residents regarding a community-based genomic cohort study. Methods: This study was conducted as a part of the health survey of the City Health Promotion section. At the conclusion of the first stage of the project, a self-administered questionnaire was mailed to a random sample of 2,500 residents in 2012. Results: The response rate was 59 % (n = 1477/2500). The findings show that 70 % of males and 50 % of females knew nothing about the project. Females and elderly people were more likely to have knowledge of the study, indicating that self-rated understanding of the terminology is statistically associated with the level of awareness regarding the project. In addition, those who were aware of the project were also aware of the benefits of research utilizing genetic information, whereas unaware respondents, particularly males, believed that unexpected negative effects may occur. Those with higher self-rated understanding of the terminology and higher awareness of benefit of the research utilizing genetic information had more positive attitudes toward undergoing drug susceptibility genetic testing, indicating that the awareness of project in females and concerns toward genetic research are not statistically associated with the willingness to undergo. Conclusions: This study suggests that a community-based genome cohort project helps raise awareness of benefit of genetic research and that knowledge, however, does not directly affect the willingness to participate in related activities, such as drug susceptibility genetic testing. Therefore, additional research that focuses on the circular relationship between risk and action must be conducted in the future. [ABSTRACT FROM AUTHOR]

Guardant360® is a commercial cancer genomic sequencing assay which covers 73 cancer related genes and provides comprehensive genomic results. This assay is minimally-invasive because it requires a simple blood specimen, and it might help us to choose matched treatments for the patients without invasive biopsy. The assay was introduced to our hospital in November 2018. We summarize the clinical utility of the results provided by Guardant360® in a Japanese local university hospital. We examined seven cases who had advanced solid cancers including small cell lung cancer (n = 1), cervical cell cancer (n = 1), ovarian cancer (n = 1), breast cancer (n = 3), gallbladder cancer (n = 1). These patients had been already treated with at least one line of chemotherapy. Physician's opinion based on the result of Guardant360® was discussed in the expert meeting before it was provided to each patient. Mean age of all patients was 66.3 years old (range; 48-76). All but one patient (85.7%) harbored actionable aberrations and the mean of detected actionable aberrations was 4.3 (range; 0-7). MSI-High was not detected in any patients. Based on these results, two patients (28.6%) were offered new therapeutic indications which were already approved in Japan, and another patient (14.3%) was suggested to be a candidate of an ongoing clinical trial of the gene specific molecular targeted therapy. Furthermore, another patient (14.3%) was identified an incidental secondary finding which was associated with the American College of Medical Genetics and Genomics guideline and the patient was recommended to have genetic counselling and further examination. In the first four months, almost one third of patients reached new treatment strategy using approved drug, and another patients offered a clinical trial based on the results of Guardant360®. Because the treatment efficacy based on the result is still unknown, further data accumulation is still needed. [ABSTRACT FROM AUTHOR]