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JOURNAL ARTICLE
MULTICENTER STUDY
RESEARCH SUPPORT, NON-U.S. GOV'T
Genetic characterization of mesenchymal, clear cell, and dedifferentiated chondrosarcoma.
Genes, Chromosomes & Cancer 2012 October
Clear cell, mesenchymal, and dedifferentiated chondrosarcoma are rare, cartilaginous tumors with limited treatment options other than surgery. Conventional chondrosarcomas have been extensively studied at the genetic level, but for rare chondrosarcoma subtypes, this is merely restricted to case reports. Information on the genetics of rare chondrosarcomas may provide insight into the etiology of these specific disease subtypes and possible alternative treatment strategies. Therefore, the aim of this study was to genetically characterize this subset of rare tumors. Using array CGH, we gathered genomic information of 30 rare cartilaginous tumors. In addition, we constructed tissue microarrays with 2 mm cores of 23 clear cell, 23 mesenchymal, and 45 dedifferentiated chondrosarcomas, in triplicate. Using immunohistochemistry, we investigated expression of R132H IDH1, and p53 and retinoblastoma pathways. Results were verified and further investigated with a methylation assay and MLPA for CDKN2A/p16, and IDH1/2, and TP53 mutation analysis. Array-CGH showed numerous genomic alterations in all subtypes. However, only a limited number of recurrent alterations were detected, none of which seemed to be associated with the subtypes. The IDH1/2, p53, and retinoblastoma pathways were affected in 0, 9, and 95% of clear cell chondrosarcomas, in 0, 39, and 70% in mesenchymal chondrosarcomas, and in 50, 59, and 85% of dedifferentiated chondrosarcomas, respectively. Our results suggest an important role for the retinoblastoma pathway in all three rare chondrosarcoma subtypes investigated.
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