{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T01:21:08Z","timestamp":1794014468972,"version":"4.8.0"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T00:00:00Z","timestamp":1629417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp; Cancer"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Familial gastrointestinal stromal tumors (GIST) are dominant genetic disorders that are caused by germline mutations of the type III receptor tyrosine kinase KIT. While sporadic mutations are frequently found in mastocytosis and GISTs, germline mutations of <jats:italic>KIT<\/jats:italic> have only been described in 39 families until now. We detected a novel germline mutation of <jats:italic>KIT<\/jats:italic> in exon 11 (p.Lys\u2010558\u2010Asn; K558N) in a patient from a kindred with several GISTs harboring different secondary somatic <jats:italic>KIT<\/jats:italic> mutations. Structural analysis suggests that the primary germline mutation alone is not sufficient to release the autoinhibitory region of KIT located in the transmembrane domain. Instead, the KIT kinase module becomes constitutively activated when K558N combines with different secondary somatic mutations. The identical germline mutation in combination with an additional somatic <jats:italic>KIT<\/jats:italic> mutation was detected in a second patient of the kindred with seminoma while a third patient within the family had a cutaneous mastocytosis. These findings suggest that the K558N mutation interferes with the juxtamembranous part of KIT, since seminoma and mastocystosis are usually not associated with exon 11 mutations.<\/jats:p>","DOI":"10.1002\/gcc.22988","type":"journal-article","created":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T11:51:40Z","timestamp":1627905100000},"page":"827-832","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The novel <scp><i>KIT<\/i><\/scp> exon 11 germline mutation <scp>K558N<\/scp> is associated with gastrointestinal stromal tumor, mastocytosis, and seminoma development"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4172-1176","authenticated-orcid":false,"given":"Michael","family":"Meir","sequence":"first","affiliation":[{"name":"Department of General, Visceral, Transplant, Vascular and Pediatric Surgery University Hospital Wuerzburg  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Maurus","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Wuerzburg  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Kuper","sequence":"additional","affiliation":[{"name":"Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Wuerzburg  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Hankir","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplant, Vascular and Pediatric Surgery University Hospital Wuerzburg  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Wardelmann","sequence":"additional","affiliation":[{"name":"Gerhard\u2010Domagk\u2010Institute of Pathology, University Hospital Muenster, Albert\u2010Schweitzer\u2010Campus 1  Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Rosenwald","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Wuerzburg  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph\u2010Thomas","family":"Germer","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplant, Vascular and Pediatric Surgery University Hospital Wuerzburg  Wuerzburg Germany"},{"name":"Comprehensive Cancer Center, Mainfranken Josef\u2010Schneider\u2010Stra\u00dfe  Wuerzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Wiegering","sequence":"additional","affiliation":[{"name":"Department of General, Visceral, Transplant, Vascular and Pediatric Surgery University Hospital Wuerzburg  Wuerzburg Germany"},{"name":"Comprehensive Cancer Center, Mainfranken Josef\u2010Schneider\u2010Stra\u00dfe  Wuerzburg 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