PMID- 21171078
OWN - NLM
STAT- MEDLINE
DCOM- 20110222
LR  - 20181201
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Linking)
VI  - 223
IP  - 3
DP  - 2011 Feb
TI  - Role of the transcription factor T (brachyury) in the pathogenesis of sporadic 
      chordoma: a genetic and functional-based study.
PG  - 327-35
LID - 10.1002/path.2816 [doi]
AB  - 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.
CI  - Copyright (c) 2010 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Presneau, Nadege
AU  - Presneau N
AD  - UCL Cancer Institute, 72 Huntley Street, London WC1 6BT, UK.
FAU - Shalaby, Asem
AU  - Shalaby A
FAU - Ye, Hongtao
AU  - Ye H
FAU - Pillay, Nischalan
AU  - Pillay N
FAU - Halai, Dina
AU  - Halai D
FAU - Idowu, Bernadine
AU  - Idowu B
FAU - Tirabosco, Roberto
AU  - Tirabosco R
FAU - Whitwell, Duncan
AU  - Whitwell D
FAU - Jacques, Thomas S
AU  - Jacques TS
FAU - Kindblom, Lars-Gunnar
AU  - Kindblom LG
FAU - Bruderlein, Silke
AU  - Bruderlein S
FAU - Moller, Peter
AU  - Moller P
FAU - Leithner, Andreas
AU  - Leithner A
FAU - Liegl, Bernadette
AU  - Liegl B
FAU - Amary, Fernanda M
AU  - Amary FM
FAU - Athanasou, Nicholas N
AU  - Athanasou NN
FAU - Hogendoorn, Pancras Cw
AU  - Hogendoorn PC
FAU - Mertens, Fredrik
AU  - Mertens F
FAU - Szuhai, Karoly
AU  - Szuhai K
FAU - Flanagan, Adrienne M
AU  - Flanagan AM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101124
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Fetal Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (T-Box Domain Proteins)
RN  - EQ43SC3GDB (Brachyury protein)
SB  - IM
CIN - J Pathol. 2011 Apr;223(5):565-6. PMID: 21394718
MH  - Animals
MH  - Cell Proliferation
MH  - Chordoma/*genetics/metabolism/pathology
MH  - Chromosome Aberrations
MH  - DNA Copy Number Variations
MH  - DNA, Neoplasm/genetics
MH  - Fetal Proteins/*genetics/metabolism
MH  - Gene Knockdown Techniques
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Mice
MH  - Mice, SCID
MH  - Neoplasm Proteins/genetics/metabolism
MH  - Neoplasm Transplantation
MH  - Polymerase Chain Reaction/methods
MH  - T-Box Domain Proteins/*genetics/metabolism
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
EDAT- 2010/12/21 06:00
MHDA- 2011/02/23 06:00
CRDT- 2010/12/21 06:00
PHST- 2010/09/09 00:00 [received]
PHST- 2010/10/05 00:00 [revised]
PHST- 2010/10/15 00:00 [accepted]
PHST- 2010/12/21 06:00 [entrez]
PHST- 2010/12/21 06:00 [pubmed]
PHST- 2011/02/23 06:00 [medline]
AID - 10.1002/path.2816 [doi]
PST - ppublish
SO  - J Pathol. 2011 Feb;223(3):327-35. doi: 10.1002/path.2816. Epub 2010 Nov 24.