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Twelve of 181 (7%) tumours displayed amplification of the <jats:italic>T<\/jats:italic> 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 <jats:italic>T<\/jats:italic> as assessed by FISH. No germline alteration of the <jats:italic>T<\/jats:italic> locus was identified in non\u2010neoplastic tissue from 40 patients. Copy number gain of <jats:italic>T<\/jats:italic> was seen in a similar percentage of sacrococcygeal, mobile spine and base of skull tumours. Knockdown of <jats:italic>T<\/jats:italic> in the cell line, U\u2010CH1, which showed polysomy of chromosome 6 involving 6q27, resulted in a marked decrease in cell proliferation and morphological features consistent with a senescence\u2010like phenotype. The U\u2010CH1 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]<jats:styled-content>$\\gamma^{\\rm{null}}$<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tex2gif-ueqn-1.gif\" xlink:title=\"equation image\"\/><\/jats:styled-content> mouse model. In conclusion, chromosomal aberrations resulting in gain of the <jats:italic>T<\/jats:italic> locus are common in sporadic chordomas and expression of this gene is critical for proliferation of chordoma cells <jats:italic>in vitro<\/jats:italic>. Copyright \u00a9 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2816","type":"journal-article","created":{"date-parts":[[2010,10,20]],"date-time":"2010-10-20T08:52:31Z","timestamp":1287564751000},"page":"327-335","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":187,"title":["Role of the transcription factor <i>T<\/i> (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional\u2010based 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