RESUMEN
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%).
Asunto(s)
Neoplasias Óseas/genética , Condrosarcoma/genética , Colágeno Tipo II/genética , Mutación , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Condrosarcoma/metabolismo , Condrosarcoma/patología , Colágeno Tipo II/metabolismo , Biología Computacional , Variaciones en el Número de Copia de ADN , Bases de Datos Genéticas , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Clasificación del Tumor , Polimorfismo de Nucleótido Simple , Proteína de Retinoblastoma/genética , Proteína de Retinoblastoma/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: To characterize HIV-1 specific CTL responses to regulatory proteins Tat and Rev in HIV-B'/C virus-infected ART-naive individuals. METHODS: HIV-1-specific CTL responses were analyzed by IFN-gamma ELISPOT assay using overlapping peptides spanning the consensus sequences of HIV-1 clade C Tat and Rev proteins. Statistical analysis and graphical presentation were performed using SIGMAPLOT 10.0 and SIGMASTAT 3.5. For samples with a positive response, the magnitude of CTL responses was compared between HIV-1 C proteins by Wilcoxon rank sum test, and the significance threshold was P<0.05. RESULTS: Tat and Rev were frequently recognized, with 23% and 52% of the tested individuals having detectable responses to these proteins, respectively. Several immunodominant regions were detected in Rev. No significant correlation was observed between the magnitude and breadth of CTL responses to regulatory proteins and the control of virus replication in this study. CONCLUSION: Tat and Rev can serve as targets for HIV-1-specific CTL, and several immunodominant regions are detectable in Rev. Further characterization of epitopes and their role in virus control may shed light on pathogenesis of HIV-1 natural infection and also be useful for the design and testing of candidate vaccines.