Loss of IDH1 and IDH2 Mutations During the Evolution of Metastatic Chondrosarcoma

Authors

William Cross
Iben Lyskjær
Christopher Davies
Abigail Bunkum
Ana Maia Rocha
Tom Lesluyes
Fernanda Amary
Roberto Tirabosco
Cristina Naceur-Lombardelli
Mariam Jamal-Hanjani
Charles Swanton
Nischalan Pillay
Simone Zaccaria
Adrienne M Flanagan
Peter Van Loo

Language

English

Publication Date

11-26-2025

Journal

Genome Biology

DOI

10.1186/s13059-025-03812-2

PMID

41299743

PMCID

PMC12659308

PubMedCentral® Posted Date

11-26-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Driver 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.

Keywords

Isocitrate Dehydrogenase, Chondrosarcoma, Humans, Mutation, Bone Neoplasms, DNA Methylation, Neoplasm Metastasis, Chondrosarcoma, Cancer evolution, IDH1, IDH2, Metastasis, Bone tumor

Published Open-Access

yes

Recommended Citation

Cross, William; Lyskjær, Iben; Davies, Christopher; et al., "Loss of IDH1 and IDH2 Mutations During the Evolution of Metastatic Chondrosarcoma" (2025). Faculty, Staff and Student Publications. 6601.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6601