Transcriptome comparison identifies potential biomarkers of spine and skull base chordomas View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2017-08-27

AUTHORS

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

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. More... »

PAGES

489-497

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00428-017-2224-x

DOI

http://dx.doi.org/10.1007/s00428-017-2224-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1091364987

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28844110


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