{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T20:19:38Z","timestamp":1783714778855,"version":"3.55.0"},"reference-count":42,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Most thyroid cancers are initiated by alterations activating the mitogen-activated protein kinase (MAPK) pathway and progress via additional genomic events. Because papillary thyroid carcinoma (PTC) generally has a favorable prognosis and rarely advances, knowledge about later-acquired genomic alterations and their impact on prognosis is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>This study is a real-world database study using a nationwide database that contains clinical data and comprehensive genomic profiling (CGP) test results. We investigated gene alterations and their impact on prognosis in advanced PTC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The study included 322 patients with advanced papillary carcinoma who underwent CGP tests for drug selection between June 2019 and April 2024. Metastases were present in 96% of cases, and 70% received systemic therapy. The most common genomic abnormalities were mutations in the\n                      <jats:italic toggle=\"yes\">TERT<\/jats:italic>\n                      promoter and\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      .\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      alterations were mutually exclusive with\n                      <jats:italic toggle=\"yes\">RBM10<\/jats:italic>\n                      and other MAPK pathway genes such as\n                      <jats:italic toggle=\"yes\">RET, NRAS,<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">NTRK1<\/jats:italic>\n                      , but co-occurred with\n                      <jats:italic toggle=\"yes\">TERT<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">AKT1<\/jats:italic>\n                      . The MAPK pathway had the highest frequency of alterations (96%), followed by the phosphoinositide 3-kinase (PI3K; 23%), cell cycle (13%), and p53 (11%) pathways. Survival analysis showed that alterations in\n                      <jats:italic toggle=\"yes\">PTEN<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">CDKN2A<\/jats:italic>\n                      were independent poor prognostic factors. Patients harboring alterations in the PI3K or cell cycle pathway showed significantly shorter overall survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Our study clarified the frequency, co-occurrence, and exclusivity of gene alterations in advanced PTC. Alterations in the PI3K or cell cycle pathways are linked to poor prognosis, and therapies targeting these pathways may warrant further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00520","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T19:59:14Z","timestamp":1783713554000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Genomic Characteristics and Prognostic Association in Advanced Papillary Thyroid Carcinoma"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2977-4419","authenticated-orcid":true,"given":"Soji","family":"Toda","sequence":"first","affiliation":[{"name":"Department of Endocrine Surgery, Kanagawa Cancer Center, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7384-3513","authenticated-orcid":true,"given":"Yukihiko","family":"Hiroshima","sequence":"additional","affiliation":[{"name":"Department of Cancer Genome Medicine, Kanagawa Cancer Center, Kanagawa, Japan"},{"name":"Division of Advanced Cancer Therapeutics, Kanagawa Cancer Center Research Institute, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9724-8525","authenticated-orcid":true,"given":"Hiroyuki","family":"Iwasaki","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, Kanagawa Cancer Center, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2576-9946","authenticated-orcid":true,"given":"Mei","family":"Kadoya","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, Kanagawa Cancer Center, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chihiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruhiko","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7079-4454","authenticated-orcid":true,"given":"Yoichiro","family":"Okubo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kanagawa Cancer Center, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-2007","authenticated-orcid":true,"given":"Aya","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Surgery, Yokohama City University, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9222-1869","authenticated-orcid":true,"given":"Katsuhiko","family":"Masudo","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, Kanagawa Cancer Center, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-023-00920-6"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0373"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14754"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-22-0417"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae271"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.035"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3774"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007752"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz972"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1015"},{"key":"e_1_3_6_12_2","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2023","unstructured":"R Core Team: R: A Language and Environment for Statistical Computing. 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