{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:43:43Z","timestamp":1792133023060,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,11,5]],"date-time":"2014-11-05T00:00:00Z","timestamp":1415145600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P01CA124570"],"award-info":[{"award-number":["P01CA124570"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000048","name":"American Cancer Society","doi-asserted-by":"publisher","award":["CRP-09-171-06-CCE"],"award-info":[{"award-number":["CRP-09-171-06-CCE"]}],"id":[{"id":"10.13039\/100000048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2015,3]]},"abstract":"\n BACKGROUND<\/jats:title>\n \n Endometrial cancer has been recognized only recently as a major component of Cowden syndrome (CS). Germline alterations in phosphatase and tensin homolog (\n PTEN<\/jats:italic>\n ;\n PTEN<\/jats:italic>\n _mut+), succinate dehydrogenase B\/C\/D (\n SDHB\u2010D<\/jats:italic>\n ;\n SDHx<\/jats:italic>\n _var+), and killin (\n KLLN<\/jats:italic>\n _Me+) cause CS and Cowden syndrome\u2013like (CSL) phenotypes. This study was aimed at identifying the prevalence and clinicopathologic predictors of germline\n PTEN<\/jats:italic>\n _mut+,\n SDHx<\/jats:italic>\n _var+, and\n KLLN<\/jats:italic>\n _Me+ in CS\/CSL patients presenting with endometrial cancer.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n PTEN<\/jats:italic>\n and\n SDHB\u2010D<\/jats:italic>\n mutation and\n KLLN<\/jats:italic>\n promoter methylation analyses were performed for 371 prospectively enrolled patients (2005\u20102011). PTEN protein was analyzed from patient\u2010derived lymphoblast lines. The\n PTEN<\/jats:italic>\n Cleveland Clinic (CC) score is a weighted, regression\u2010based risk calculator giving the a priori risk for\n PTEN<\/jats:italic>\n _mut+. Demographic and clinicopathologic features were correlated with the specific gene.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Germline\n PTEN<\/jats:italic>\n _mut+,\n SDHx<\/jats:italic>\n _var+, and\n KLLN<\/jats:italic>\n _Me+ were found in 7%, 9.8%, and 10.5% of informative samples, respectively. Predictors of\n PTEN<\/jats:italic>\n _mut+ included an age\u2009\u2264\u200950 years (odds ratio [OR] for an age\u2009<\u200930 years, 6.1 [\n P<\/jats:italic>\n \u2009=\u2009.015]; OR for an age of 30\u201050 years, 4.4 [\n P<\/jats:italic>\n \u2009=\u2009.001]), macrocephaly (OR, 14.4;\n P<\/jats:italic>\n \u2009<\u2009.001), a higher CC score (OR for a 1\u2010U increment, 1.35;\n P<\/jats:italic>\n \u2009<\u2009.001), a PTEN protein level within the lowest quartile (OR, 5.1;\n P<\/jats:italic>\n \u2009=\u2009.039), and coexisting renal cancer (OR, 5.7;\n P<\/jats:italic>\n \u2009=\u2009.002).\n KLLN<\/jats:italic>\n _Me+ patients were on average 8 years younger than\n KLLN<\/jats:italic>\n _Me\u2013 patients (44 vs 52 years,\n P<\/jats:italic>\n \u2009=\u2009.018). Predictors of\n KLLN<\/jats:italic>\n _Me+ were a younger age and a higher CC score. On the other hand, no clinical predictors of\n SDH<\/jats:italic>\n _var+ were found.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n \n Clinical predictors of\n PTEN<\/jats:italic>\n and\n KLLN<\/jats:italic>\n alterations, but not\n SDHx<\/jats:italic>\n _var+, were identified. These predictors should alert the treating physician to potential heritable risk and the need for referral to genetic professionals. High\u2010risk cancer surveillance and prophylactic surgery of the uterus may be considered for\n KLLN<\/jats:italic>\n _Me+ patients similarly to\n PTEN<\/jats:italic>\n _mut+ patients.\n \n Cancer<\/jats:italic>\n 2015;121:688\u2013696.\n <\/jats:bold>\n \u00a9\n 2014 American Cancer Society<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cncr.29106","type":"journal-article","created":{"date-parts":[[2014,11,5]],"date-time":"2014-11-05T14:19:01Z","timestamp":1415197141000},"page":"688-696","source":"Crossref","is-referenced-by-count":59,"title":["Germline\n \n PTEN<\/i>\n <\/scp>\n ,\n \n SDHB\u2010D<\/i>\n <\/scp>\n , and\n \n KLLN<\/i>\n <\/scp>\n alterations in endometrial cancer patients with Cowden and Cowden\u2010like syndromes: An international, multicenter, prospective study"],"prefix":"10.1002","volume":"121","author":[{"given":"Haider","family":"Mahdi","sequence":"first","affiliation":[{"name":"Section of Gynecologic Oncology\/ObGyn and Women's Health Institute, Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica L.","family":"Mester","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily A.","family":"Nizialek","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Ngeow","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Michener","sequence":"additional","affiliation":[{"name":"Section of Gynecologic Oncology\/ObGyn and Women's Health Institute, Cleveland Clinic Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charis","family":"Eng","sequence":"additional","affiliation":[{"name":"Genomic Medicine Institute, Cleveland Clinic Cleveland Ohio"},{"name":"Lerner Research Institute, Cleveland Clinic Cleveland Ohio"},{"name":"Taussig Cancer Institute, Cleveland Clinic Cleveland Ohio"},{"name":"Stanley Shalom Zielony Institute of Nursing Excellence, Cleveland Clinic Cleveland Ohio"},{"name":"Department of Genetics and Genome Sciences Case Western Reserve University School of Medicine Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21166"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-2283"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.11.013"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.3.507"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200289"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.1877"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr459"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020152"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/321282"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5454.848"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/81551"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)07110-0"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21004"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gnf056"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/521051"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1086\/377109"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30493"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0769"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.11.924"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm662"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507816102"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.5.6.12228"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2944"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2008.07.011"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.29106","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.29106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T16:18:15Z","timestamp":1760285895000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.29106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,5]]},"references-count":24,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1002\/cncr.29106"],"URL":"https:\/\/doi.org\/10.1002\/cncr.29106","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,5]]}}}