Establishment and characterization of TK-DDCS1: a novel IDH1 mutated dedifferentiated chondrosarcoma cell line

Dedifferentiated chondrosarcoma (DDCS) is a rare and aggressive subtype of chondrosarcoma, characterized by the coexistence of a high-grade spindle or pleomorphic tumor that lacks a substantial cartilaginous matrix. Notably, it shows a mutant IDH1 incidence of over 80%. This study established a novel DDCS cell line with an IDH1 mutation, TK-DDCS1, derived from the right ilium of a 67-year-old Japanese female patient. TK-DDCS1 cells maintain the undifferentiated DDCS phenotype with the IDH1p.R132L mutation. The IDH1R132 mutation is known to be associated with a poor prognosis for chondrosarcoma, and the p.R132L mutation is a novel variant among the registered DDCS cell lines in the Cellosaurus database. The mutant IDH1 inhibitor, DS-1001b, inhibited the proliferation of TK-DDCS1 in a dose-dependent manner in both two-dimensional and spheroid cultures. The tumorigenicity of TK-DDCS1 was demonstrated through xenografting into EGFP-transgenic BALB/c Rag2-/-/Jak3-/- (EGFP-BRJ) mice, where the tumors exhibited undifferentiated phenotypes of DDCS in both morphological and immunohistochemical features. Thus, TK-DDCS1 serves as a valuable model for investigating the characteristics of DDCS and exploring molecular targeted therapies.