{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T02:02:39Z","timestamp":1793325759152,"version":"4.5.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,7]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract.<\/jats:title>\n                    <jats:p>\n                      An intriguing feature of autosomal dominant polycystic kidney disease (ADPKD) is the focal and sporadic formation of renal and extrarenal cysts. Recent documentation of somatic\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      mutations in cystic epithelia of patients with germ-line\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      mutations suggests a \u201ctwo-hit\u201d model for cystogenesis in type 1 ADPKD. This study tests whether the same mechanism for cystogenesis might also occur in type 2 ADPKD. Genomic DNA was obtained from 54 kidney and liver cysts from three patients with known germ-line\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      mutations, using procedures that minimize contamination of cells from noncystic tissue. Using intragenic and microsatellite markers, these cyst samples were screened for loss of heterozygosity. The same samples were also screened for somatic mutations in five of the 15 exons in\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      by single-stranded conformational polymorphism analysis. Loss of heterozygosity was found in five cysts, and unique intragenic mutations were found in seven other cysts. In 11 of these 12 cysts, it was also determined that the somatic mutation occurred nonrandomly in the copy of\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      inherited from the unaffected parent. These findings support the \u201ctwo-hit\u201d model as a unified mechanism for cystogenesis in ADPKD. In this model, the requirement of a somatic mutation as the rate-limiting step for individual cyst formation has potential therapeutic implications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.v1071524","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T12:13:13Z","timestamp":1620216793000},"page":"1524-1529","source":"Crossref","is-referenced-by-count":143,"title":["Somatic PKD2 Mutations in Individual Kidney and Liver Cysts Support a \u201cTwo-Hit\u201d Model of Cystogenesis in Type 2 Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1681","volume":"10","author":[{"given":"YORK","family":"PEI","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TERRY","family":"WATNICK","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NING","family":"HE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KAIRONG","family":"WANG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YAN","family":"LIANG","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PATRICK","family":"PARFREY","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GREGORY","family":"GERMINO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PETER ST.","family":"GEORGE-HYSLOP","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-199907000-00013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:24:52Z","timestamp":1786130692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-199907000-00013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,7]]},"references-count":0,"journal-issue":{"issue":"7","published-print":{"date-parts":[[1999]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.v1071524","relation":{},"ISSN":["1046-6673"],"issn-type":[{"value":"1046-6673","type":"print"}],"subject":[],"published":{"date-parts":[[1999,7]]}}}