Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
Nat Genet. 2013 Aug;45(8):923-6. doi: 10.1038/ng.2668. Epub 2013 Jun 16.
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%).
软骨肉瘤是一组异质性的恶性骨肿瘤，是仅次于骨肉瘤的第二大常见原发性骨恶性肿瘤。最近的研究表明，近一半的中心性软骨肉瘤中存在 IDH1 或 IDH2 的频繁、反复突变。然而，对这种肿瘤类型的系统基因组分析很少，因此，其他基因的作用尚不清楚。在这里，我们报告了 49 名软骨肉瘤（病例）患者的综合基因组分析。我们发现主要软骨胶原基因 COL2A1 的高突变率，在 37%的病例中发现了插入、缺失和重排。突变模式与选择可能损害正常胶原生物合成的变异一致。此外，我们还发现了 IDH1 或 IDH2（59%）、TP53（20%）、RB1 通路（33%）和 Hedgehog 信号通路（18%）的突变。
