Loss of IDH1 and IDH2 mutations during the evolution of metastatic chondrosarcoma.
journal contribution
posted on 2025-12-02, 14:02 authored by William Cross, Iben Lyskjær, Christopher Davies, Abigail Bunkum, Ana Maia Rocha, Tom Lesluyes, Fernanda Amary, Roberto Tirabosco, Cristina Naceur-Lombardelli, PEACE consortium, Mariam Jamal-Hanjani, Charles Swanton, Nischalan Pillay, Simone Zaccaria, Adrienne M Flanagan, Peter Van LooDriver mutations in IDH1 and IDH2 are initiating events in the evolution of chondrosarcoma and several other cancer types. Here, we present evidence that mutant IDH1 is recurrently lost in metastatic central chondrosarcoma. This may reflect either relaxed positive selection for the mutant IDH1 locus, or negative selection for the hypermethylation phenotype later in tumor evolution. This finding highlights the challenge for therapeutic intervention by mutant IDH1 inhibitors in chondrosarcoma.
