Developmental gene expression in skull-base chordomas and chondrosarcomas
Cas Vanderheijden1,2, Youssef Yakkioui2,3, Thomas Vaessen2,4
1Department of Neurosurgery, Maastricht University Medical Center, P. Debyelaan 25, 6202 AZ, Maastricht, The Netherlands.
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.
Insights
This study identified key developmental genes, including Brachyury, CD24, chordin, HOXA5, and ACAN, that are differentially expressed in chordoma compared to chondrosarcoma. These findings may aid in diagnosing and treating these axial spine and skull base tumors.
Area of Science:
- Oncology
- Developmental Biology
- Genetics
Background:
- Chordomas and chondrosarcomas are malignant tumors of the axial spine and skull base with differing origins.
- Chordomas arise from notochordal remnants, while chondrosarcomas originate from mesenchymal cells.
- Accurate differentiation is critical for treatment and prognosis due to chordomas' poor treatment response.
Purpose of the Study:
- To evaluate the differential expression of developmental transcription factors in skull base chordomas and chondrosarcomas.
- To identify genes associated with notochord, mesoderm, and axial spine development that distinguish between these two tumor types.
Main Methods:
- Histopathologically confirmed biopsies from 12 chordoma and 7 chondrosarcoma patients.
- RNA extraction followed by real-time quantitative PCR (RT-qPCR) analysis.
- Evaluation of 32 evolutionary conserved genes, normalized to ACTB and RS27a housekeeping genes.
Main Results:
- Fifteen genes showed exclusive or overexpression in chordoma compared to chondrosarcoma.
- Brachyury and CD24 were highly and exclusively expressed in chordoma.
- Novel genes exclusive to chordomas included chordin, HOXA5, and ACAN; ten genes were differentially expressed in chondrosarcoma.
Conclusions:
- Differential expression of chordin, HOXA5, ACAN, and CD24 may be relevant to chordoma pathophysiology.
- These genes could hold diagnostic and therapeutic value for chordoma patients.
- Further research into the role of these genes in tumorigenesis is warranted.
More Related Videos
07:26Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
Published on: April 1, 2022
07:00Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas
Published on: February 28, 2019
