Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study
Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study
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DOI：
10.1002/path.2816
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发表时间：
2011-02-01
影响因子：
7.3
通讯作者：
Flanagan, Adrienne M.
中科院分区：
文献类型：
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作者：
Presneau, Nadege;Shalaby, Asem;Flanagan, Adrienne M.
对181例脊索瘤患者进行了荧光原位杂交（FISH）、定量PCR （qPCR）和阵列CGH （aCGH）等多种分析。181例肿瘤中有12例（7%）显示T位点扩增，另外2例显示局灶扩增；70/181（39%）肿瘤为6号染色体多体，8/181（4.5%）原发性肿瘤显示少量T等位基因增加。在40例患者的非肿瘤组织中未发现T位点的种系改变。在骶尾骨、活动脊柱和颅底肿瘤中，T的拷贝数增加的比例相似。在6号染色体涉及6q27的多体细胞系U-CH1中，T的敲低导致细胞增殖明显减少，形态学特征与衰老样表型一致。在NOD/SCID/白细胞介素2受体[IL2r] γ (null)小鼠模型中，U-CH1细胞系表现出典型的脊索瘤形态和免疫组织化学特征，通过异种移植物的产生证实了U-CH1细胞系代表脊索瘤。总之，染色体畸变导致T位点的增加在散发性脊索瘤中很常见，该基因的表达对体外脊索瘤细胞的增殖至关重要。版权所有(C) 2010英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
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.