Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Presneau, N; Shalaby, A; Ye, H; Pillay, N; Halai, D; Idowu, B; Tirabosco, R; Whitwell, D; Jacques, TS; Kindblom, LG; Brüderlein, S; Möller, P; Leithner, A; Liegl, B; Amary, FM; Athanasou, NN; Hogendoorn, PC; Mertens, F; Szuhai, K; Flanagan, AM.
Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study.
J Pathol. 2011; 223(3): 327-335.
Doi: 10.1002/path.2816
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Leithner Andreas
- Liegl-Atzwanger Bernadette
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Proliferation -
- Chordoma - genetics
- Chromosome Aberrations -
- DNA Copy Number Variations -
- DNA, Neoplasm - genetics
- Fetal Proteins - genetics
- Gene Knockdown Techniques -
- Genetic Predisposition to Disease -
- Humans -
- In Situ Hybridization, Fluorescence -
- Mice -
- Mice, SCID -
- Neoplasm Proteins - genetics
- Neoplasm Transplantation -
- Polymerase Chain Reaction - methods
- T-Box Domain Proteins - genetics
- Transplantation, Heterologous -
- Tumor Cells, Cultured -
- Find related publications in this database (Keywords)
- chordoma
- T
- amplification
- copy number gain
- oncogene