Virchows Archiv

, Volume 472, Issue 3, pp 489–497 | Cite as

Transcriptome comparison identifies potential biomarkers of spine and skull base chordomas

  • Achim H. Bell
  • Franco DeMonte
  • Shaan M. Raza
  • Laurence D. Rhines
  • Claudio E. Tatsui
  • Victor G. Prieto
  • Gregory N. Fuller
  • Diana Bell
Original Article

Abstract

Chordomas are rare, slowly growing, locally aggressive bone neoplasms that arise from embryonic remnants of the notochord, showing dual epithelial-mesenchymal differentiation. The high plasticity probably is the main reason for the high variety in phenotypes of chordoma, from its high heterogeneity on a cellular level to its subtype variations depending on tissue location, with its potential to develop from an inactive quiescent form to an aggressive cancer with extreme adaptability and resistance to drugs and other treatments. Gene expression profiles of formalin-fixed, paraffin-embedded skull chordoma, spine chordoma, and normal tissue specimens were generated and compared. Using strict criteria, we identified 222 differentially expressed transcripts unique to skull base chordoma, 261 unique to spine chordoma, and 192 common to both chordoma subtypes. Further analysis of these three groups of transcripts allowed the selection of three subsets of highly differentially expressed genes as potential biomarkers, disease drivers, and therapeutic targets in both chordoma subtypes. Immunohistochemistry revealed LMX1A to be dominant in skull base chordoma, SALL3 to be unique to spine chordoma, and T to be common to both chordoma subtypes. In both chordoma subtypes, the genes with the highest expression were predominantly development-related genes, mostly transcription factors. Our findings indicate that these developmental genes play important oncogenic roles in chordoma, mainly causing high plasticity and resistance to therapy in both these cancer subtypes but also determining their differentiation status and proliferation activity, pointing to features expected of heterogeneous stem cell-like tissues with similarities to their notochord origins.

Keywords

Chordoma Skull base Spine Transcriptome Developmental genes Stem cells Plasticity 

Notes

Funding source

This study was supported by start-up funds from MD Anderson (DB) and presented at AACR Advances in Sarcoma, Philadelphia May 2017.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag GmbH Deutschland 2017

Authors and Affiliations

  1. 1.Pathology DepartmentThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Head and Neck Surgery DepartmentThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Pathology Research DepartmentThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Neurosurgery DepartmentThe University of Texas MD Anderson Cancer CenterHoustonUSA

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