{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T19:16:01Z","timestamp":1788030961387,"version":"build-2784847793"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010484","name":"American Head and Neck Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010484","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["K08DE034837"],"award-info":[{"award-number":["K08DE034837"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["Dean's Scholars Award from the Washington University Division of Physician\u2010Scientists"],"award-info":[{"award-number":["Dean's Scholars Award from the Washington University Division of Physician\u2010Scientists"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Develop a preoperative risk classifier for guiding the extent of surgery in differentiated thyroid carcinomas (DTCs) under 4\u2009cm.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>In silico study, validation with retrospective cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Genomic data repositories, academic tertiary medical center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prognostic transcriptional groups and American Thyroid Association (ATA) risk groups in The Cancer Genome Atlas (TCGA) were used to create novel Clinico\u2010TRanscriptomic (CTR) groups. Differential gene expression (DGE) was performed. Consensus clustering was used to assess the reproducibility of genomic and histologic features in: (1) Bethesda V\/VI fine\u2010needle aspirates (FNA) from the Afirma Genomic Sequencing Classifier (GSC) database (GC cohort); (2) thyroid carcinomas annotated by ATA histopathologic risk group (surgical cohort); (3) independent surgical cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Within TCGA (n\u2009=\u2009451), CTR\u2010Low was enriched with\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      mutations. CTR\u2010Intermediate was enriched in follicular cancers, while CTR\u2010High had high rates of\n                      <jats:italic>TERT<\/jats:italic>\n                      promoter (\n                      <jats:italic>TERT<\/jats:italic>\n                      p) and\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      mutations. A 144 gene classifier (PreOperative INdicator of Thyroid cancer progression [POINT]) was developed based on inter\u2010CTR DGEs. Clustering of the GC cohort using POINT demonstrated similar genomic features with 3 groups characterized by\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      and\n                      <jats:italic>ALK\/NTRK\/RET<\/jats:italic>\n                      fusions,\n                      <jats:italic>RAS<\/jats:italic>\n                      mutations, or\n                      <jats:italic>TERT<\/jats:italic>\n                      p\/\n                      <jats:italic>BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      alterations. Agreement of POINT with ATA risk group in the surgical cohort (n\u2009=\u2009129) showed fair agreement (weighted\n                      <jats:italic>\u03ba<\/jats:italic>\n                      \u2009=\u20090.25), NPV 0.89 for ruling out high ATA risk, and NNT 5.3 to avoid 1 completion thyroidectomy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The POINT classifier is predictive of genomic alterations and ATA risk in independent data sets. This study advances precision oncology, shifting the paradigm from size\u2010based toward individualized, biology\u2010driven care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ohn.70333","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T09:49:03Z","timestamp":1783676943000},"page":"578-586","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of Novel mRNA Classifiers to Stratify Preoperative Thyroid Tumor Risk"],"prefix":"10.1002","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-1404","authenticated-orcid":false,"given":"Thomas F.","family":"Barrett","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Jama","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Alshalalfa","sequence":"additional","affiliation":[{"name":"Veracyte Inc. South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Tharakan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Hao","sequence":"additional","affiliation":[{"name":"Veracyte Inc. South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Klopper","sequence":"additional","affiliation":[{"name":"Veracyte Inc. South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor B.","family":"Cavazos","sequence":"additional","affiliation":[{"name":"Veracyte Inc. South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan S.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine St. Louis Missouri USA"},{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at the Siteman Cancer Center Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Pipkorn","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine St. Louis Missouri USA"},{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at the Siteman Cancer Center Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason T.","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine St. Louis Missouri USA"},{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at the Siteman Cancer Center Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Zolkind","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine St. Louis Missouri USA"},{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at the Siteman Cancer Center Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Adkins","sequence":"additional","affiliation":[{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at the Siteman Cancer Center Washington University School of Medicine St. Louis Missouri USA"},{"name":"Division of Oncology Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Oppelt","sequence":"additional","affiliation":[{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at the Siteman Cancer Center Washington University School of Medicine St. Louis Missouri USA"},{"name":"Division of Oncology Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Apicelli","sequence":"additional","affiliation":[{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at the Siteman Cancer Center Washington University School of Medicine St. Louis Missouri USA"},{"name":"Department of Radiation Oncology Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Rammohan","sequence":"additional","affiliation":[{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at the Siteman Cancer Center Washington University School of Medicine St. Louis Missouri USA"},{"name":"Department of Radiation Oncology Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor C.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Surgery, Section of Surgical Oncology Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidharth V.","family":"Puram","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Washington University School of Medicine St. Louis Missouri USA"},{"name":"Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at the Siteman Cancer Center Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Jasim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology Washington University School of Medicine St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4695-6142","authenticated-orcid":false,"given":"R. 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