Retrospective study of survival impact of IDH2 and TP53 mutations in patients with chondrosarcoma

Chondrosarcoma (CS) has a prognosis largely influenced by tumor grade. A retrospective study at two centers in Germany investigated prognostic relevance of tumor-specific mutations in CS.The study included 109 patients (53 females and 56 males, median age at time of surgery 57 years, range 16-89). The tumor grades were G1/atypical cartilaginous tumors (39%), G2 (41%), and G3/dedifferentiated (10%). Tumor-specific mutations, including IDH, TP53, TERT promoter, and CDKN2A/B were identified through DNA isolation and next-generation sequencing. Median follow-up was 3.8 years with mortality of 17%. IDH mutations were detected in 59% (IDH1 64%, IDH2 36%), with dedifferentiated CS showing highest IDH mutation rate (91%). IDH2 mutations were associated with significantly worse disease-specific survival compared with IDH wild-type or IDH1 mutations, independent of tumor grade. In multivariable analysis, IDH2 and TP53 mutations were independent predictors of worse survival. The authors conclude that IDH2 and TP53 mutations are enriched in dedifferentiated CS and are significant independent predictors of worse survival, regardless of tumor grade.