Chondrosarcoma is a heterogeneous collection of malignant bone tumors and is the second most common primary malignancy of bone after osteosarcoma. Recent work has identified frequent, recurrent mutations in IDH1 or IDH2 in nearly half of central chondrosarcomas. However, there has been little systematic genomic analysis of this tumor type, and, thus, the contribution of other genes is unclear. Here we report comprehensive genomic analyses of 49 individuals with chondrosarcoma (cases). We identified hypermutability of the major cartilage collagen gene COL2A1, with insertions, deletions and rearrangements identified in 37% of cases. The patterns of mutation were consistent with selection for variants likely to impair normal collagen biosynthesis. In addition, we identified mutations in IDH1 or IDH2 (59%), TP53 (20%), the RB1 pathway (33%) and Hedgehog signaling (18%).

Original publication

DOI

10.1038/ng.2668

Type

Journal article

Journal

Nat Genet

Publication Date

08/2013

Volume

45

Pages

923 - 926

Keywords

Bone Neoplasms, Chondrosarcoma, Collagen Type II, Computational Biology, DNA Copy Number Variations, Databases, Genetic, Hedgehog Proteins, Humans, Mutation, Neoplasm Grading, Polymorphism, Single Nucleotide, Retinoblastoma Protein, Signal Transduction