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Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study

Presneau, Nadege; Shalaby, Asem; Ye, Hongtao; Pillay, Nischalan; Halai, Dina; Idowu, Bernadine; Tirabosco, Roberto; Whitwell, Duncan; Jacques, Thomas S. and Kindblom, Lars-Gunnar, et al. (2011) In Journal of Pathology 223(3). p.327-335
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... (More)
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]gamma(null) 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. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. (Less)
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publication status
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keywords
copy number gain, amplification, chordoma, T, oncogene
in
Journal of Pathology
volume
223
issue
3
pages
327 - 335
publisher
John Wiley & Sons
external identifiers
  • wos:000285427200001
  • scopus:78650597625
ISSN
0022-3417
DOI
10.1002/path.2816
language
English
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yes
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b898fb3a-340b-4df1-818e-084c32071a66 (old id 1773853)
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2011-02-01 10:39:14
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2017-10-22 03:18:40
@article{b898fb3a-340b-4df1-818e-084c32071a66,
  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]gamma(null) 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. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.},
  author       = {Presneau, Nadege and Shalaby, Asem and Ye, Hongtao and Pillay, Nischalan and Halai, Dina and Idowu, Bernadine and Tirabosco, Roberto and Whitwell, Duncan and Jacques, Thomas S. and Kindblom, Lars-Gunnar and Bruederlein, Silke and Moeller, Peter and Leithner, Andreas and Liegl, Bernadette and Amary, Fernanda M. and Athanasou, Nicholas N. and Hogendoorn, Pancras C. W. and Mertens, Fredrik and Szuhai, Karoly and Flanagan, Adrienne M.},
  issn         = {0022-3417},
  keyword      = {copy number gain,amplification,chordoma,T,oncogene},
  language     = {eng},
  number       = {3},
  pages        = {327--335},
  publisher    = {John Wiley & Sons},
  series       = {Journal of Pathology},
  title        = {Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study},
  url          = {http://dx.doi.org/10.1002/path.2816},
  volume       = {223},
  year         = {2011},
}