Mutational analysis of primary and advanced chordoma tissue using next‐generation sequencing

作者：Josh Chan, Joseph K. Kendal, Zhenfeng Duan, Al Ferreira, Alireza Samiei, Scott D. Nelson, Arun S. Singh, Elizabeth L. Lord, Brooke Crawford, Nicholas M. Bernthal, Francis J. Hornicek · 发表于：Cancer · 年份：2025 · DOI：10.1002/cncr.70033 · 被引用次数：6 · 研究领域：Bone Tumor Diagnosis and Treatments、Sarcoma Diagnosis and Treatment、Oral and Maxillofacial Pathology

BACKGROUND: Chordomas are rare ectodermal bone malignancies derived from transformed notochordal remnants. Histologic variants include conventional (80%-90%), chondroid (5%-15%), and dedifferentiated (2%-8%). Because chordomas are relatively resistant to chemotherapy and radiotherapy, novel targeted agents are needed to expand treatment approaches and improve outcomes. This study analyzes the genomic landscape of chordoma and identifies potential pathogenic and druggable targets. METHODS: Eighty-six tumor samples derived from chordoma patients treated at Massachusetts General Hospital, University of California, Los Angeles, and the University of Miami were included. Tumor specimens were sent for comprehensive molecular profiling using next-generation sequencing. The most frequently mutated genes were identified and categorized by subtype, and microsatellite instability and programmed death ligand-1 (PD-L1) staining were assessed. RESULTS: Histologic subtypes included 70 conventional (81.4%), nine chondroid (10.5%), and seven dedifferentiated chordomas (8.1%). The most common mutations were cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) (28 of 86, 33%), low-density lipoprotein receptor-related protein 1B (10 of 86, 12%), polybromo-1 (9 of 86, 11%), and epidermal growth factor receptor (EGFR) (8 of 86, 9%). By subtype, CDKN2A/B mutation was most common in conventional chordoma (24 of 70, 34%), and chondroid chordoma (3 of 9, 33%). CDKN2A/B and EGFR mutations were most common...