The present data strongly suggest that inhibition of mutant IDH1 is a promising therapeutic approach in chondrosarcoma, particularly for the treatment of relapsed or dedifferentiated chondrosarcoma.
Similar to other IDH-mutated tumor types, IDH-mutated DDCHS also show elevated 2HG level, indicating that the oncometabolite activity of 2HG may contribute to DDCHS oncogenesis and progression.
Identification of IDH1 or IDH2 mutations supports the diagnosis of dedifferentiated chondrosarcoma rather than UPS of bone while also providing some insight into the pathogenesis of these 2 lesions.
Deep parallel sequencing of the dedifferentiated component showed a nonsynonymous mutation at exon 4 of IDH1 gene at codon R132 leading to a substitution of arginine, with serine confirming glandular differentiation in dedifferentiated chondrosarcoma.
The presence of IDH1/2 mutations can also help confirm the diagnosis of dedifferentiated chondrosarcoma when the tumor displays osteosarcomatous differentiation.