{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:34:09Z","timestamp":1774085649565,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T00:00:00Z","timestamp":1544572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370073"],"award-info":[{"award-number":["81370073"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802528"],"award-info":[{"award-number":["81802528"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003347","name":"Fudan University","doi-asserted-by":"publisher","award":["YJJQ201802"],"award-info":[{"award-number":["YJJQ201802"]}],"id":[{"id":"10.13039\/501100003347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>An inherited susceptibility to renal cancers is associated with multiple predisposing genes, but most screening tests are limited to patients with a family history. Next\u2010generation sequencing (NGS)\u2013based multigene panels provide an efficient and adaptable tool for investigating pathogenic germline mutations on a larger scale. This study investigated the frequency of pathogenic germline mutations in renal cancer predisposition genes in patients with sporadic, early\u2010onset disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An NGS\u2010based panel of 23 known and potential renal cancer predisposition genes was used to analyze germline mutations in 190 unrelated Chinese patients under the age of 45 years who presented with renal tumors. The detected variants were filtered for pathogenicity, and then their frequencies were calculated and correlated with clinical features. Germline variants of the fumarate hydratase (\n                      <jats:italic>FH<\/jats:italic>\n                      ) and BRCA1\u2010associated protein 1 (\n                      <jats:italic>BAP1<\/jats:italic>\n                      ) genes were comprehensively analyzed because of their aggressive potential.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 18 patients (9.5%) had germline mutations in 10 genes. Twelve of these 18 patients had alterations in renal cancer predisposition genes (6.3%), and 6 patients had mutations in potential predisposition genes such as\n                      <jats:italic>BRCA1<\/jats:italic>\n                      \/\n                      <jats:italic>2<\/jats:italic>\n                      . Notably, pathogenic mutation carriers had a significant family history in second\u2010degree relatives in comparison with those without pathogenic mutations (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a0.001). Variants of unknown clinical significance in\n                      <jats:italic>FH<\/jats:italic>\n                      and\n                      <jats:italic>BAP1<\/jats:italic>\n                      demonstrated evidence of additional somatic loss in tumors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In patients with early\u2010onset disease, a multigene panel identified a high pathogenic germline mutation rate in renal cancer predisposition genes. This study emphasizes the importance of screening patients with early\u2010onset disease for mutations in cancer predisposition genes. Germline screening should be encouraged in early\u2010onset patients to provide personalized medicine and improve patient outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.31908","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T11:51:38Z","timestamp":1544615498000},"page":"1060-1069","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Germline mutations of renal cancer predisposition genes and clinical relevance in Chinese patients with sporadic, early\u2010onset disease"],"prefix":"10.1002","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4125-7975","authenticated-orcid":false,"given":"Junlong","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center Shanghai People's Republic of China"},{"name":"Department of Oncology Shanghai Medical College, Fudan University Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongkai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center Shanghai People's Republic of China"},{"name":"Department of Oncology Shanghai Medical College, Fudan University Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Ricketts","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youfeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria J.","family":"Merino","sequence":"additional","affiliation":[{"name":"Urologic Oncology Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center Shanghai People's Republic of China"},{"name":"Department of Oncology Shanghai Medical College, Fudan University Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guohai","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Urology Fudan University Shanghai Cancer Center Shanghai People's Republic of China"},{"name":"Department of Oncology Shanghai Medical College, Fudan University Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hualei","family":"Gan","sequence":"additional","affiliation":[{"name":"Department of Oncology Shanghai Medical College, Fudan University Shanghai People's Republic of China"},{"name":"Department of Pathology Fudan University Shanghai Cancer Center Shanghai People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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