{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T10:15:30Z","timestamp":1779963330392,"version":"3.53.1"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Clear cell chondrosarcoma (CCC) is a rare, low\u2010grade malignant bone tumor and a specific subtype of chondrosarcoma. In contrast to conventional central chondrosarcoma, which often exhibits recurrent\n                      <jats:italic>IDH1\/2<\/jats:italic>\n                      mutations, CCC is IDH\u2010wildtype, and its genomic profile remains uncharacterized. Sporadic cases have been described in association with von Hippel\u2013Lindau (VHL) disease, but somatic\n                      <jats:italic>VHL<\/jats:italic>\n                      alterations have not been demonstrated in this tumor.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 35\u2010year\u2010old man presented with local recurrence of a distal femoral tumor 5\u2009years after curettage and allograft reconstruction for a tumor that was initially diagnosed as clear cell chondrosarcoma. The recurrent tumor was resected and analyzed using a comprehensive DNA\/RNA next\u2010generation sequencing assay with matched germline testing to distinguish somatic from germline alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The recurrent tumor measured 5.0\u2009cm and showed classic CCC morphology with focal areas of conventional chondrosarcoma\u2010like differentiation. No\n                      <jats:italic>IDH1\/2<\/jats:italic>\n                      mutations were identified. Two pathogenic loss\u2010of\u2010function variants were detected:\n                      <jats:italic>COL2A1<\/jats:italic>\n                      c.1262_1266+2delinsTCC (variant allele frequency [VAF], 34%) and\n                      <jats:italic>VHL<\/jats:italic>\n                      c.341\u20102A&gt;C (VAF, 45%). The tumor had a low tumor mutational burden, low loss of heterozygosity, and a complex karyotype with monosomy of chromosome 3. Gene expression profiling revealed decreased VHL mRNA expression. Germline testing showed no germline\n                      <jats:italic>VHL<\/jats:italic>\n                      alteration, confirming somatic VHL inactivation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>To our knowledge, this report is the first to describe a molecularly profiled CCC with somatic VHL inactivation. These results expand the evolving genomic spectrum of CCC beyond its previously known IDH\u2010wildtype status and suggest that VHL pathway dysregulation may contribute to tumorigenesis in a subset of cases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/gcc.70130","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T13:38:32Z","timestamp":1777988312000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clear Cell Chondrosarcoma With Somatic\n                    <scp>VHL<\/scp>\n                    Inactivation: A Case Report With Integrated Genomic and Transcriptomic Analysis"],"prefix":"10.1002","volume":"65","author":[{"given":"Lalit R.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology and Imaging Sciences Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shervin","family":"Oskouei","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8515-2649","authenticated-orcid":false,"given":"Armita","family":"Bahrami","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478\u2010198403000\u201000009"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2023.06.004"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2913"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.21974"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.13952"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26041542"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15092556"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689\u2010019\u201000149\u20101"},{"issue":"2","key":"e_1_2_6_10_1","first-page":"266","article-title":"Clear Cell Chondrosarcoma of the Talus in Von Hippel\u2010Lindau Disease: A Rare Tumor in an Unusual Location and Uncommon Co\u2010Presentation","volume":"13","author":"Song M. 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