{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:40:27Z","timestamp":1787920827405,"version":"build-2784847793"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,10,29]],"date-time":"2018-10-29T00:00:00Z","timestamp":1540771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parathyroid carcinoma (PC) is a rare endocrine malignancy that can cause life-threatening hypercalcemia. We queried whether comprehensive genomic profiling (CGP) of PC might identify genomic alterations (GAs), which would suggest benefit from rationally matched therapeutics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed hybrid-capture-based CGP to identify GAs and tumor mutational burden (TMB) in tumors from patients with this malignancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There were 85 total GAs in 16 cases (5.3 GAs per case), and the median TMB was 1.7 mutations per megabase (m\/Mb), with three cases having &amp;gt;20 m\/Mb (18.7%). The genes most frequently harboring GA were CDC73 (38%), TP53 (38%), and MEN1 (31%). All MEN1-mutated cases also had loss of heterozygosity at that locus, but in contrast all CDC73-mutated cases retained heterozygosity. GAs suggesting potential benefit from matched targeted therapy were identified in 11 patients (69%) and most frequently found in PTEN (25%), NF1 (12.5%), KDR (12.5%), PIK3CA (12.5%), and TSC2 (12.5%). A patient whose tumor harbored KDR T668 K and who was treated with cabozantinib experienced a &amp;gt; 50% drop in parathyroid hormone level and radiographic partial response of 5.4 months with duration limited by toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CGP identified GAs in PC that suggest benefit from targeted therapy, as supported by an index case of response to a matched tyrosine kinase inhibitor. Moreover, the unexpectedly high frequency of high TMB (&amp;gt;20 m\/Mb) suggests a subset of PC may benefit from immune checkpoint inhibitors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.2018-0334","type":"journal-article","created":{"date-parts":[[2018,10,29]],"date-time":"2018-10-29T10:15:38Z","timestamp":1540808138000},"page":"791-797","source":"Crossref","is-referenced-by-count":66,"title":["Genomic Profiling of Parathyroid Carcinoma Reveals Genomic Alterations Suggesting Benefit from Therapy"],"prefix":"10.1093","volume":"24","author":[{"given":"Hyunseok","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA"},{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, 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