Transcriptome comparison identifies potential biomarkers of spine and skull base chordomas.

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...

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Publicado en:Virchows Archiv: European Journal of Pathology Vol. 472; no. 3; pp. 489 - 498
Autores principales: Bell, Achim H., DeMonte, Franco, Raza, Shaan M., Rhines, Laurence D., Tatsui, Claudio E., Prieto, Victor G., Fuller, Gregory N., Bell, Diana
Formato: research Journal Article
Publicado: Springer Nature Mar2018
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Mar2018
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      pub: Springer Nature
      place: New York, New York
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        atl: Transcriptome comparison identifies potential biomarkers of spine and skull base chordomas.
      aug:
        au:
          Bell, Achim H.
          DeMonte, Franco
          Raza, Shaan M.
          Rhines, Laurence D.
          Tatsui, Claudio E.
          Prieto, Victor G.
          Fuller, Gregory N.
          Bell, Diana
        affil: Pathology Department, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA
      sug:
        subj:
          Spinal Neoplasms
          Skull Metabolism
          Neoplasms, Germ Cell and Embryonal
          Skull Neoplasms
          Gene Expression Profiling
          Skull Neoplasms Metabolism
          Spinal Neoplasms Metabolism
          Human
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
      ab: 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.
      pubtype: Academic Journal
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        research
        Journal Article
      ougenre: Article
    language: English
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