{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:14:20Z","timestamp":1778649260832,"version":"3.51.4"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>RET<\/jats:italic>\n                      fusions represent a subgroup of alterations in cancer biology that exhibit sensitivity to selective RET kinase inhibitors. We analytically validated a next-generation sequencing-based companion diagnostic (CDx) to detect\n                      <jats:italic>RET<\/jats:italic>\n                      fusions in solid tumors via a comprehensive genomic profiling assay, FoundationOne\n                      <jats:sup>\u00ae<\/jats:sup>\n                      CDx (F1CDx\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The F1CDx assay produces chimeric read pairs to determine fusion status. Additionally, a study of F1CDx was conducted as a retrospective clinical bridging study based on LIBRETTO-001 clinical trial samples and data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across solid tumor types, F1CDx demonstrated a high concordance for\n                      <jats:italic>RET<\/jats:italic>\n                      fusion detection with both an externally validated assay and LIBRETTO-001 clinical trial assays with positive percent agreements of 100.0% (146\/146) and 90.80% (79\/87), negative percent agreements of 97.3% (254\/261) and 100.0% (138\/138), and overall percent agreements of 98.2% (400\/407) and 96.44% (213\/225), respectively. Based on LIBRETTO-001 clinical data, the objective response rate to selpercatinib for patients with tumors harboring\n                      <jats:italic>RET<\/jats:italic>\n                      fusions as determined by F1CDx was estimated to be 69.62%. Demonstrated analytical and clinical performance of F1CDx led to the pan-tumor approvals from the U.S. Food and Drug Administration (FDA) in 2023 and the Japan Ministry of Health, Labour and Welfare (MHLW) in 2024 of F1CDx to identify\n                      <jats:italic>RET<\/jats:italic>\n                      fusions in solid tumor patients for treatment with selpercatinib.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      F1CDx is an accurate, reliable, FDA- and MHLW-approved method for the pan-tumor identification of\n                      <jats:italic>RET<\/jats:italic>\n                      fusions for treatment with selpercatinib.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1820286","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:46:25Z","timestamp":1778647585000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pan-tumor validation of FoundationOne\u00aeCDx as a companion diagnostic for RET fusions as a predictor of response to selpercatinib"],"prefix":"10.3389","volume":"16","author":[{"given":"Allison","family":"van den Hout","sequence":"first","affiliation":[{"name":"Foundation Medicine, Inc.","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard S. P.","family":"Huang","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc.","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caleb","family":"Ho","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc.","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc.","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas A.","family":"Mata","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc.","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baljinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc.","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sameera R.","family":"Wijayawardana","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company","place":["Indianapolis, IN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Wright","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company","place":["Indianapolis, IN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna M.","family":"Szpurka","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company","place":["Indianapolis, IN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas I.","family":"Lin","sequence":"additional","affiliation":[{"name":"Foundation Medicine, Inc.","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3680","article-title":"Ret revisited: expanding the oncogenic portfolio","volume":"14","author":"Mulligan","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-023-00347-2","article-title":"Genomic landscape of 891 RET fusions detected across diverse solid tumor types","volume":"7","author":"Parimi","year":"2023","journal-title":"NPJ Precis Oncol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/his.14082","article-title":"Recurrent RET gene fusions in pediatric spindle mesenchymal neoplasms","volume":"76","author":"Davis","year":"2020","journal-title":"Histopathology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgz184","article-title":"Retoma: a cancer subtype with a shared driver 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