Subject(s)
Chordoma/metabolism , Fetal Proteins/biosynthesis , Gene Expression Regulation, Neoplastic , Membrane Proteins/metabolism , Osteosarcoma/metabolism , T-Box Domain Proteins/biosynthesis , Blotting, Western , Chordoma/genetics , Fetal Proteins/genetics , Humans , Immunohistochemistry , Membrane Proteins/genetics , Osteosarcoma/genetics , Reverse Transcriptase Polymerase Chain Reaction , T-Box Domain Proteins/genetics , Tissue Array AnalysisABSTRACT
A variety of analyses, including fluorescence in situ hybridization (FISH), quantitative PCR (qPCR) and array CGH (aCGH), have been performed on a series of chordomas from 181 patients. Twelve of 181 (7%) tumours displayed amplification of the T locus and an additional two cases showed focal amplification; 70/181 (39%) tumours were polysomic for chromosome 6, and 8/181 (4.5%) primary tumours showed a minor allelic gain of T as assessed by FISH. No germline alteration of the T locus was identified in non-neoplastic tissue from 40 patients. Copy number gain of T was seen in a similar percentage of sacrococcygeal, mobile spine and base of skull tumours. Knockdown of T in the cell line, U-CH1, which showed polysomy of chromosome 6 involving 6q27, resulted in a marked decrease in cell proliferation and morphological features consistent with a senescence-like phenotype. The U-CH1 cell line was validated as representing chordoma by the generation of xenografts, which showed typical chordoma morphology and immunohistochemistry in the NOD/SCID/interleukin 2 receptor [IL2r]gammanull mouse model. In conclusion, chromosomal aberrations resulting in gain of the T locus are common in sporadic chordomas and expression of this gene is critical for proliferation of chordoma cells in vitro.
