{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:36:36Z","timestamp":1783701396080,"version":"3.55.0"},"reference-count":25,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n            <jats:title>PURPOSE<\/jats:title>\n            <jats:p>\n              Germline likely pathogenic and pathogenic variants (LPV\/PVs) in\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              have been associated with an increased risk of various cancers including angiosarcoma, melanoma, glioma, thyroid cancer, and chronic lymphocytic leukemia (CLL). However, to date, most of the published data regarding\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              PVs involve cohorts of patients selected for specific cancer types, or stem from commercial laboratory cohorts from patients selected for germline clinical testing, which may cause ascertainment biases. The objective was to identify germline\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              variants in a pan-cancer cohort and describe the associated phenotypes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS<\/jats:title>\n            <jats:p>\n              Germline exome data available for 19,315 patients with cancer from the Oncology Research Information Exchange Network (ORIEN) were assessed for\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              LPV\/PV. Data regarding cancer diagnoses were obtained for those with and without\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              variants. Associations were assessed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS<\/jats:title>\n            <jats:p>\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              LPV\/PVs were identified in 23 patients. The cancer types seen in more than one patient include CLL (n = 7), papillary thyroid cancer (PTC, n = 5), colorectal cancer (n = 3), lung cancer (n = 3), glioblastoma (n = 2), and neuroendocrine tumors (n = 2). Compared with\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              -negative patients, those with\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              LPV\/PVs were 5.5-fold more likely to be diagnosed with PTC (95% CI, 1.9 to 15.1;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .004) and 16.6-fold more likely to be diagnosed with CLL (95% CI, 6.4 to 41.9;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt; .001). Patients with\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              LPV\/PVs had a younger median age of first cancer diagnosis compared with\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              -negative patients (\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              = .008).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSION<\/jats:title>\n            <jats:p>\n              To our knowledge, this study is the largest investigation of\n              <jats:italic toggle=\"yes\">POT1<\/jats:italic>\n              germline variants in a pan-cancer cohort. We identify and confirm specific associations with CLL and PTC in this cohort. Differences in results between analysis of largely unselected cohorts compared with clinical testing cohorts highlight the need to study gene-cancer associations in more unselected populations.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1200\/po-24-00946","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T19:59:13Z","timestamp":1752091153000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Germline\n            <i>POT1<\/i>\n            Variants in a Pan-Cancer Cohort"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1549-5363","authenticated-orcid":true,"given":"Pamela L.","family":"Brock","sequence":"first","affiliation":[{"name":"Division of Human Genetics, The Ohio State University College of Medicine, Comprehensive Cancer Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan","family":"Webster","sequence":"additional","affiliation":[{"name":"Maternal Fetal Medicine, Legacy Health, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1857-5246","authenticated-orcid":true,"given":"Sandya","family":"Liyanarachchi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Therapeutics, The Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7131-5331","authenticated-orcid":true,"given":"Lindsey","family":"Byrne","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, The Ohio State University College of Medicine, Comprehensive Cancer Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dale J.","family":"Hedges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2625-313X","authenticated-orcid":true,"given":"Pat","family":"Gulhati","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Rutgers Cancer Institute, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2314-0164","authenticated-orcid":true,"given":"J. Kevin","family":"Hicks","sequence":"additional","affiliation":[{"name":"Department of Pathology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3656-2470","authenticated-orcid":true,"given":"Carlos H.F.","family":"Chan","sequence":"additional","affiliation":[{"name":"Holden Comprehensive Cancer Center, University of Iowa Health Care, Iowa City, IA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenan","family":"Onel","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6584-1818","authenticated-orcid":true,"given":"Leigh Anne","family":"Stout","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-9239","authenticated-orcid":true,"given":"Whitney","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine Cooper","family":"Pickarski","sequence":"additional","affiliation":[{"name":"Markey Cancer Center, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2372-0372","authenticated-orcid":true,"given":"Juvianee","family":"Estrada-Veras","sequence":"additional","affiliation":[{"name":"Murtha Cancer Center Research Program, Department of Surgery, Uniformed Service University of the Health Sciences, Bethesda, MD"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD"},{"name":"Walter Reed National Military Medical Center, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3843-3621","authenticated-orcid":true,"given":"Bodour","family":"Salhia","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Norris Comprehensive Cancer Center, Keck School of Medicine of University of Southern California, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisen","family":"Axell","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Holman","sequence":"additional","affiliation":[{"name":"Division of Gynecologic Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9493-7894","authenticated-orcid":true,"given":"Mohamed H.","family":"Abdel-Rahman","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Departments of Ophthalmology and Internal Medicine, The Ohio State University, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew D.","family":"Ringel","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Therapeutics, The Ohio State University College of Medicine, Columbus, OH"},{"name":"The Ohio State University Comprehensive Cancer Center, Columbus, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1060036"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2020.02.002"},{"key":"e_1_3_7_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1346005"},{"key":"e_1_3_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2584"},{"key":"e_1_3_7_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-010422-091101"},{"key":"e_1_3_7_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2024.04.006"},{"key":"e_1_3_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2947"},{"key":"e_1_3_7_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2941"},{"key":"e_1_3_7_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2022-108776"},{"key":"e_1_3_7_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2020-107098"},{"key":"e_1_3_7_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9383"},{"key":"e_1_3_7_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/dju384"},{"key":"e_1_3_7_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-695692"},{"key":"e_1_3_7_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2300503"},{"key":"e_1_3_7_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061441"},{"key":"e_1_3_7_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11883"},{"key":"e_1_3_7_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.039"},{"key":"e_1_3_7_19_2","doi-asserted-by":"crossref","unstructured":"Freed D Aldana R Weber JA Edwards JS. 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