An integrated clinical genomic and transcriptomic subgrouping of central chondrosarcoma

Chondrosarcoma, a malignant cartilage-producing bone tumor, is the second most-common bone sarcoma. Chondrosarcomas are histologically graded, which is so far the best predictor of survival. Early mutations in isocitrate dehydrogenase (IDH)-1 and -2 genes are frequent, leading to the production of the oncometabolite D-2-hydroxyglutarate, which affects DNA methylation, resulting in a preferred chondrogenic differentiation over osteogenic differentiation of mesenchymal stem cells, which are currently considered the precursor cells of chondrosarcomas. DNA methylation profiling has previously revealed distinct profiles between IDH mutant and wild-type chondrosarcomas, but the presence of further DNA methylation subgroups indicates that classification based solely on IDH status is too simplistic. In this study, we aim to identify biological subgroups in chondrosarcomas by combining clinical data, IDH mutation status, gene expression and genome wide loss of heterozygosity (gwLOH). Overall design: Tumors of 54 patients with chondrosarcoma (ACT, grade 2, grade 3 and dedifferentiatied chondrosarcoma)