The driver landscape of sporadic chordoma

Nat Commun. 2017 Oct 12;8(1):890. doi: 10.1038/s41467-017-01026-0.

Abstract

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms / genetics*
  • Case-Control Studies
  • Cell Line, Tumor
  • Chordoma / genetics*
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Fetal Proteins / genetics*
  • Gene Duplication
  • Humans
  • Mutation*
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Polymorphism, Single Nucleotide
  • T-Box Domain Proteins / genetics*
  • Vesicular Transport Proteins / genetics*

Substances

  • Fetal Proteins
  • LYST protein, human
  • T-Box Domain Proteins
  • Vesicular Transport Proteins
  • PIK3R1 protein, human
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Brachyury protein