{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T04:58:56Z","timestamp":1780894736487,"version":"3.54.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), with hypophysitis being a serious endocrine toxicity that often requires hormone replacement and poses a risk of adrenal crisis. Biomarkers for predicting ICI-induced hypophysitis are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective, single-center cohort study used the Research Patient Data Registry (RPDR) to identify adults with breast cancer, lung cancer, renal cell carcinoma, or melanoma who received PD-1 inhibitor monotherapy (pembrolizumab or nivolumab) between January 1, 2000, and May 29, 2024. The final cohort included 82 patients with available tumor genomic profiling data, including 26 who developed hypophysitis and 56 matched PD-1 inhibitor-treated controls who did not develop hypophysitis. Tumor mutational burden (TMB) and tumor gene mutation profiles were compared between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Genomic analysis showed that the hypophysitis group had a higher overall tumor mutational burden (6.02 vs. 5.19 mut\/Mb,\n                      <jats:italic>P<\/jats:italic>\n                      =\u00a00.002). Furthermore, we identified significantly high rate of mutations in the genes\n                      <jats:italic>BABAM1<\/jats:italic>\n                      (18.2% vs. 0%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.014),\n                      <jats:italic>KDM5C<\/jats:italic>\n                      (18.2% vs. 0%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.014),\n                      <jats:italic>CDH4<\/jats:italic>\n                      (19.2% vs. 1.8%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.018), and\n                      <jats:italic>TAL1<\/jats:italic>\n                      (19.2% vs. 1.8%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.018) in the hypophysitis group. In contrast,\n                      <jats:italic>PAXIP1<\/jats:italic>\n                      mutations were more common in the non-hypophysitis group (19.6% vs. 0%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.037), suggesting a potential protective role.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This exploratory study identifies a tumor genomic profile associated with PD-1 inhibitor-related hypophysitis. Higher TMB and enrichment of selected tumor mutations may reflect a tumor immunogenicity state that predisposes to pituitary autoimmunity under PD-1 blockade. These findings provide a hypothesis-generating genomic framework for future studies of endocrine irAE risk stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1845186","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T04:23:50Z","timestamp":1780892630000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association between tumor genomic mutations and the risk of PD-1 inhibitor-induced hypophysitis: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuanyuan","family":"Zheng","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]},{"name":"Department of Geriatric Medicine, Fujian Key Laboratory of Geriatrics Diseases, Fujian Provincial Center for Geriatrics, Fujian Provincial 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