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Transcriptome comparison identifies potential biomarkers of spine and skull base chordomas

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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.

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Funding source

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

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Authors and Affiliations

  1. Pathology Department, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

    Achim H. Bell, Victor G. Prieto, Gregory N. Fuller & Diana Bell

  2. Head and Neck Surgery Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Franco DeMonte, Shaan M. Raza & Diana Bell

  3. Pathology Research Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Achim H. Bell

  4. Neurosurgery Department, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Franco DeMonte, Shaan M. Raza, Laurence D. Rhines & Claudio E. Tatsui

Authors
  1. Achim H. Bell
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  2. Franco DeMonte
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  3. Shaan M. Raza
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  4. Laurence D. Rhines
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  5. Claudio E. Tatsui
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  6. Victor G. Prieto
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  7. Gregory N. Fuller
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  8. Diana Bell
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Correspondence to Diana Bell.

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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.

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The authors declare that they have no conflict of interest.

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Bell, A.H., DeMonte, F., Raza, S.M. et al. Transcriptome comparison identifies potential biomarkers of spine and skull base chordomas. Virchows Arch 472, 489–497 (2018). https://doi.org/10.1007/s00428-017-2224-x

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  • DOI: https://doi.org/10.1007/s00428-017-2224-x

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