T (brachyury) gene duplication confers major susceptibility to familial chordoma

Nat Genet. 2009 Nov;41(11):1176-8. doi: 10.1038/ng.454. Epub 2009 Oct 4.


Using high-resolution array-CGH, we identified unique duplications of a region on 6q27 in four multiplex families with at least three cases of chordoma, a cancer of presumed notochordal origin. The duplicated region contains only the T (brachyury) gene, which is important in notochord development and is expressed in most sporadic chordomas. Our findings highlight the value of screening for complex genomic rearrangements in searches for cancer-susceptibility genes.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chordoma / genetics*
  • Chromosomes, Human, Pair 6
  • Comparative Genomic Hybridization
  • Fetal Proteins / genetics*
  • Gene Duplication*
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Polymorphism, Single Nucleotide
  • T-Box Domain Proteins / genetics*


  • Fetal Proteins
  • T-Box Domain Proteins
  • Brachyury protein