Spinal column chordoma: Prognostic significance of clinical variables and T (brachyury) gene SNP rs2305089 for local recurrence and overall survival

Chetan Bettegowda*, Stephen Yip, Sheng Fu Larry Lo, Charles G. Fisher, Stefano Boriani, Laurence D. Rhines, Joanna Y. Wang, Aron Lazary, Marco Gambarotti, Wei Lien Wang, Alessandro Luzzati, Mark B. Dekutoski, Mark H. Bilsky, Dean Chou, Michael G. Fehlings, Edward F. McCarthy, Nasir A. Quraishi, Jeremy J. Reynolds, Daniel M. Sciubba, Richard P. WilliamsJean Paul Wolinsky, Patricia L. Zadnik, Ming Zhang, Niccole M. Germscheid, Vasiliki Kalampoki, Peter Pal Varga, Ziya L. Gokaslan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Background: Chordomas are rare, locally aggressive bony tumors associated with poor outcomes. Recently, the single nucleotide polymorphism (SNP) rs2305089 in the T (brachyury) gene was strongly associated with sporadic chordoma development, but its clinical utility is undetermined. Methods: In 333 patients with spinal chordomas, we identified prognostic factors for local recurrence-free survival (LRFS) and overall survival and assessed the prognostic significance of the rs2305089 SNP. Results: The median LRFS was 5.2 years from the time of surgery (95% CI: 3.8-6.0); greater tumor volume (≥100cm3) (hazard ratio [HR] = 1.99, 95% CI: 1.26-3.15, P =.003) and Enneking inappropriate resections (HR = 2.35, 95% CI: 1.37-4.03, P =.002) were independent predictors of LRFS. The median overall survival was 7.0 years (95% CI: 5.8-8.4), and was associated with older age at surgery (HR = 1.11 per 5-year increase, 95% CI: 1.02-1.21, P =.012) and previous surgical resection (HR = 1.73, 95% CI: 1.03-2.89, P =.038). One hundred two of 109 patients (93.6%) with available pathologic specimens harbored the A variant at rs2305089; these patients had significantly improved survival compared with those lacking the variant (P = .001), but there was no association between SNP status and LRFS (P = .876). Conclusions: The ability to achieve a wide en bloc resection at the time of the primary surgery is a critical preoperative consideration, as subtotal resections likely complicate later management. This is the first time the rs2305089 SNP has been implicated in the prognosis of individuals with chordoma, suggesting that screening all patients may be instructive for risk stratification.

Original languageEnglish (US)
Pages (from-to)405-413
Number of pages9
Issue number3
StatePublished - Mar 1 2017


  • Brachyury
  • Chordoma
  • Rs2305089
  • SNP
  • Spine
  • T gene

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research


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