{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:16:34Z","timestamp":1785550594005,"version":"3.56.0"},"reference-count":17,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Genetic Testing and Molecular Biomarkers"],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"\n Background:<\/jats:title>\n Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with a high rate of germline predisposition. Although multigene panel testing (MGPT) using next-generation sequencing (NGS) is widely adopted globally, its clinical application in Japan remains limited. Methods: We developed a custom amplicon-based NGS panel targeting 12 established PPGL susceptibility genes. Germline analysis was performed in 23 Japanese patients with confirmed PPGL to evaluate sequencing quality and variant detection.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Sequencing quality was consistently high (Q30 > 96%, mapping rate >99%, on-target rate >80%), with nearly all exons (148\/149) achieving >1,000\u00d7 coverage. Pathogenic or likely pathogenic variants were found in 21.7% (5\/23), including\n SDHB<\/jats:italic>\n ,\n VHL<\/jats:italic>\n , and\n RET<\/jats:italic>\n . In addition, variants of uncertain significance (VUS) were found in 17.4% (4\/23), including novel missense variants in\n FH<\/jats:italic>\n ,\n SDHA<\/jats:italic>\n , and\n MAX<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n This study demonstrates the feasibility and clinical utility of amplicon-based MGPT for PPGL in a real-world Japanese setting and highlights the importance of ongoing VUS reclassification to improve clinical interpretation. The findings support its diagnostic value, reflect underlying clinical demand, and contributed to its non-insured clinical adoption at certified laboratories in Japan.<\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/19450265251382504","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T14:29:17Z","timestamp":1758896957000},"page":"290-293","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Germline Multigene Panel Testing in Japanese Patients with Pheochromocytoma and Paraganglioma: Technical Feasibility and Clinical Utility"],"prefix":"10.1177","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3389-9832","authenticated-orcid":false,"given":"Masato","family":"Yonamine","sequence":"first","affiliation":[{"name":"Laboratory of Laboratory\/Sports Medicine, Institute of Medicine, University of Tsukuba, Tsukuba, Japan."},{"name":"LSI Medience Corporation, Itabashi, Japan."},{"name":"Doctoral Program in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Koyanagi","sequence":"additional","affiliation":[{"name":"LSI Medience Corporation, Itabashi, Japan."},{"name":"Tsukuba i-Laboratory LLP, Tsukuba, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyo","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Tsukuba i-Laboratory LLP, Tsukuba, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Aita","sequence":"additional","affiliation":[{"name":"Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Takekoshi","sequence":"additional","affiliation":[{"name":"Laboratory of Laboratory\/Sports Medicine, Institute of Medicine, University of Tsukuba, Tsukuba, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"e_1_3_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.08.005"},{"key":"e_1_3_6_3_1","doi-asserted-by":"publisher","DOI":"10.4161\/fly.19695"},{"key":"e_1_3_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.01.001"},{"key":"e_1_3_6_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgac014"},{"key":"e_1_3_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_3_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2017.01.011"},{"key":"e_1_3_6_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa502"},{"key":"e_1_3_6_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-1498"},{"key":"e_1_3_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2016.10.002"},{"key":"e_1_3_6_11_1","unstructured":"National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u00ae) Neuroendocrine and Adrenal Tumors Version 2. 2025. Available from: https:\/\/www.nccn.org\/guidelines\/category_1 [Last accessed: Aug24 2025]."},{"key":"e_1_3_6_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab019"},{"key":"e_1_3_6_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0973-5"},{"key":"e_1_3_6_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163962"},{"key":"e_1_3_6_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2015.00092"},{"key":"e_1_3_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.185"},{"key":"e_1_3_6_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13164014"},{"key":"e_1_3_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-024-01263-4"}],"container-title":["Genetic Testing and Molecular Biomarkers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/19450265251382504","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19450265251382504","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19450265251382504","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:21:38Z","timestamp":1777447298000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/19450265251382504"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":17,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10,1]]}},"alternative-id":["10.1177\/19450265251382504"],"URL":"https:\/\/doi.org\/10.1177\/19450265251382504","relation":{},"ISSN":["1945-0265","1945-0257"],"issn-type":[{"value":"1945-0265","type":"print"},{"value":"1945-0257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]}}}