{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:32:36Z","timestamp":1790674356899,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,2,15]],"date-time":"2018-02-15T00:00:00Z","timestamp":1518652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K11020"],"award-info":[{"award-number":["16K11020"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:p>Although hereditary kidney cancer syndrome accounts for approximately five percent of all kidney cancers, the mechanistic insight into tumor development in these rare conditions has provided the foundation for the development of molecular targeting agents currently used for sporadic kidney cancer. In the late 1980s, the comprehensive study for hereditary kidney cancer syndrome was launched in the National Cancer Institute, <jats:styled-content style=\"fixed-case\">USA<\/jats:styled-content> and the first kidney cancer\u2010associated gene, <jats:italic><jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content><\/jats:italic>, was identified through kindred analysis of von Hippel\u2010Lindau (<jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content>) syndrome in 1993. Subsequent molecular studies on <jats:italic><jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content><\/jats:italic> function have elucidated that the <jats:styled-content style=\"fixed-case\">VHL<\/jats:styled-content> protein is a component of E3 ubiquitin ligase complex for hypoxia\u2010inducible factor (<jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>), which provided the basis for the development of tyrosine kinase inhibitors targeting the <jats:italic><jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PDGF<\/jats:styled-content><\/jats:italic> pathway. Recent whole\u2010exome sequencing analysis of sporadic kidney cancer exhibited the recurrent mutations in chromatin remodeling genes and the later study has revealed that several chromatin remodeling genes are altered in kidney cancer kindred at the germline level. To date, more than 10 hereditary kidney cancer syndromes together with each responsible gene have been characterized and most of the causative genes for these genetic disorders are associated with either metabolism or epigenome regulation. In this review article, we describe the molecular mechanisms of how an alteration of each kidney cancer\u2010associated gene leads to renal tumorigenesis as well as denote therapeutic targets elicited by studies on hereditary kidney cancer.<\/jats:p>","DOI":"10.1111\/cas.13503","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T00:06:56Z","timestamp":1515715616000},"page":"581-586","source":"Crossref","is-referenced-by-count":22,"title":["Hereditary kidney cancer syndromes: Genetic disorders driven by alterations in metabolism and epigenome regulation"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8211-8835","authenticated-orcid":false,"given":"Hisashi","family":"Hasumi","sequence":"first","affiliation":[{"name":"Department of Urology Yokohama City University Yokohama 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