Genomic Characterization of Chondrosarcoma Reveals Potential Therapeutic Targets

作者：Michael J. Wagner, Erica Pimenta, Nathan W. Sweeney, Elizabeth T. Loggers, Jesse L. Roberts, Elyse J. Brinkmann, Eleanor Y. Chen, Robert W. Ricciotti, Candace L. Haddox, R J Berg, Binyam Yilma, Melissa C. Stoppler, James L. Chen, Lee D. Cranmer · 发表于：JCO Precision Oncology · 年份：2025 · DOI：10.1200/po-24-00592 · 被引用次数：10 · 研究领域：Bone Tumor Diagnosis and Treatments、Sarcoma Diagnosis and Treatment、Musculoskeletal synovial abnormalities and treatments

PURPOSE Chondrosarcomas are rare cancers of cartilage with limited systemic therapy options. To identify potential therapeutic targets, this study investigated the molecular and immune landscape of three chondrosarcoma subtypes using a large database of clinical-grade sequencing results. METHODS Deidentified records from patients with a histologic diagnosis of conventional, dedifferentiated, or mesenchymal chondrosarcoma sequenced by the Tempus xT DNA assay were included. Microsatellite instability (MSI) and tumor mutational burden (TMB) were determined from sequencing data. The expression of PD-L1 and mismatch repair enzymes was evaluated in cases with available immunohistochemistry (IHC) data. RESULTS Of the 149 patients, 103 had conventional chondrosarcoma, 31 dedifferentiated chondrosarcoma, and 15 mesenchymal chondrosarcoma. Across the cohort, 44% (n = 65) had an IDH1 or IDH2 mutation. No cases were MSI high. One conventional chondrosarcoma patient had a TMB >10 mut/Mb. Among 112 patients with available PD-L1 IHC, 10% of conventional (n = 7), 45% of dedifferentiated (n = 13), and 17% of mesenchymal cases (n = 2) were PD-L1–positive. The most common somatic alterations were in IDH1 (34%) and TP53 (28%) in conventional chondrosarcoma; TP53 (68%), TERT (65%), IDH1 (39%), IDH2 (39%), CDKN2A (35%), and CDKN2B (35%) in dedifferentiated chondrosarcoma; and HEY1-NCOA2 fusions (87%) and CDKN2A (20%) in mesenchymal chondrosarcoma. MTAP was deleted in >10% of each subtype, an...