{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:42:38Z","timestamp":1791380558893,"version":"4.3.3"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Autosomal dominant polycystic kidney disease (ADPKD) is a ciliopathy caused by mutations in\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      that is characterized by renal tubular epithelial cell proliferation and progressive CKD. Although the molecular mechanisms involved in cystogenesis are not established, concurrent inactivating constitutional and somatic mutations in ADPKD genes in cyst epithelium have been proposed as a cellular recessive mechanism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We characterized, by whole-exome sequencing (WES) and long-range PCR techniques, the somatic mutations in\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      genes in renal epithelial cells from 83 kidney cysts obtained from nine patients with ADPKD, for whom a constitutional mutation in\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      was identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Complete sequencing data by long-range PCR and WES was available for 63 and 65 cysts, respectively. Private somatic mutations of\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      were identified in all patients and in 90% of the cysts analyzed; 90% of these mutations were truncating, splice site, or in-frame variations predicted to be pathogenic mutations. No\n                      <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                      -heterozygous mutations of\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      genes were identified. Copy number changes of\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      ranging from 151 bp to 28 kb were observed in 12% of the cysts. WES also identified significant mutations in 53 non-\n                      <jats:italic toggle=\"yes\">PKD1\/2<\/jats:italic>\n                      genes, including other ciliopathy genes and cancer-related genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings support a cellular recessive mechanism for cyst formation in ADPKD caused primarily by inactivating constitutional and somatic mutations of\n                      <jats:italic toggle=\"yes\">PKD1<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">PKD2<\/jats:italic>\n                      in kidney cyst epithelium. The potential interactions of these genes with other ciliopathy- and cancer-related genes to influence ADPKD severity merits further evaluation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2017080878","type":"journal-article","created":{"date-parts":[[2018,7,24]],"date-time":"2018-07-24T17:18:56Z","timestamp":1532452736000},"page":"2139-2156","source":"Crossref","is-referenced-by-count":67,"title":["Somatic Mutations in Renal Cyst Epithelium in Autosomal Dominant Polycystic Kidney Disease"],"prefix":"10.1681","volume":"29","author":[{"given":"Adrian Y.","family":"Tan","sequence":"first","affiliation":[{"name":"Departments of Pathology and Laboratory Medicine,"},{"name":"Microbiology and Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Microbiology and 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