Developmental gene expression in skull-base chordomas and chondrosarcomas

Cas Vanderheijden, Youssef Yakkioui, Thomas Vaessen, Remco Santegoeds, Yasin Temel, Govert Hoogland, Koos Hovinga*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose Chordomas are malignant tumors of the axial spine and skull base, and they are notorious for their poor treatment response. Differentiating these tumors from comparatively less malignant chondrosarcomas is crucial for treatment and prognostication. Both tumor types differ in their developmental origin. Chordomas are considered to be derived from notochordal remnants and chondrosarcomas from mesenchymal cells. Here, we evaluated the differential expression of developmental transcription factors in these skull base tumors.Methods Histopathologically-confirmed tumor biopsies were obtained from 12 chordoma and 7 chondrosarcoma patients. Following RNA extraction, samples were submitted to real-time quantitative PCR (RT-qPCR) for the evaluation of 32 evolutionary conserved genes that are known to associate with notochord, mesoderm, and axial spine development. Gene expression levels were normalized to housekeeping genes ACTB and RS27a.Results Fifteen genes were either exclusively expressed (n = 12) or overexpressed (n = 3; 2.21-4.43 fold increase) in chordoma, compared to chondrosarcoma. Brachyury and CD24 were highly and exclusively expressed in chordoma. Other novel genes exclusive to chordomas included chordin, HOXA5 and ACAN. Vice versa, ten genes were either exclusively expressed (n = 2) or overexpressed (n = 8; 0.01-0.66 fold increase) in chondrosarcoma, compared to chordoma.Conclusion As chordoma patients demonstrate a worse prognosis compared to chondrosarcoma patients, the differential expression of chordin, HOXA5 and ACAN and CD24 could be relevant for the pathophysiology of chordomas and may have diagnostic and treatment value. Further study on role of these genes in tumorigenesis is therefore warranted.
Original languageEnglish
Number of pages8
JournalJournal of Neuro-Oncology
DOIs
Publication statusE-pub ahead of print - 1 Dec 2024

Keywords

  • Chordoma
  • Chondrosarcoma
  • HoxA5
  • Chordin
  • ACAN
  • SOX9
  • BRACHYURY
  • TRANSCRIPTION
  • REGULATOR
  • AGGRECAN

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