+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

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

Journal of Pathology 223(3): 327-335

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.

(PDF emailed within 0-6 h: $19.90)

Accession: 055614625

Download citation: RISBibTeXText

PMID: 21171078

DOI: 10.1002/path.2816

Related references

The embryonic transcription factor Brachyury confers chordoma chemoresistance via upregulating CA9. American Journal of Translational Research 10(3): 936-947, 2018

Phase I Study of a Poxviral TRICOM-Based Vaccine Directed Against the Transcription Factor Brachyury. Clinical Cancer Research 23(22): 6833-6845, 2017

Brachyury gene copy number gain and activation of the PI3K/Akt pathway: association with upregulation of oncogenic Brachyury expression in skull base chordoma. Journal of Neurosurgery: 1-10, 2017

An integrated functional genomics approach identifies the regulatory network directed by brachyury (T) in chordoma. Journal of Pathology 228(3): 274-285, 2013

Phase I Trial of a Yeast-Based Therapeutic Cancer Vaccine (GI-6301) Targeting the Transcription Factor Brachyury. Cancer Immunology Research 3(11): 1248-1256, 2016

Revisiting chordoma with brachyury, a "new age" marker: analysis of a validation study on 51 cases. Archives of Pathology & Laboratory Medicine 134(8): 1181-1187, 2010

The role of epidermal growth factor receptor in chordoma pathogenesis: a potential therapeutic target. Journal of Pathology 223(3): 336-346, 2011

Possible pathogenic role of redox factor-1 and the AP-1 transcription factor components in sporadic inclusion-body myositis. Neurology 54(7 Supp 3): A241-A242, April 11, 2000

The Role of EGFR, Hepatocyte Growth Factor Receptor (c-Met), c-ErbB2 (HER2-neu) and Clinicopathological Parameters in the Pathogenesis and Prognosis of Chordoma. Turk Patoloji Dergisi 33(2): 112-120, 2017

An approach to predict transcription factor DNA binding site specificity based upon gene and transcription factor functional categorization. Bioinformatics 23(18): 2449-2454, 2007

The Brachyury protein: a T-domain transcription factor. Seminars in Developmental Biology. Dec; 66: 395-403, 1995

The T protein encoded by Brachyury is a tissue-specific transcription factor. Embo Journal 14(19): 4763-4772, 1995

Expression of Brachyury-like T-box transcription factor, Xbra3 in Xenopus embryo. Development Genes and Evolution 209(9): 560-563, 1999

T-box transcription factor brachyury is associated with prostate cancer progression and aggressiveness. Clinical Cancer Research 20(18): 4949-4961, 2015

Crystallographic structure of the T domain-DNA complex of the Brachyury transcription factor. Nature (London) 389(6653): 884-888, 1997