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Updated: Sep 11, 2025
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Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
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Mutational analysis of primary and advanced chordoma tissue using next-generation sequencing
Josh Chan1, Joseph K Kendal1,2, Zhenfeng Duan3
1Department of Surgery, Section of Orthopaedic Surgery, University of Calgary, Calgary, Alberta, Canada.
Cancer
|August 13, 2025
Summary
This study reveals common genetic mutations in chordoma, a rare bone cancer. Identifying these genomic alterations, such as CDKN2A/B and EGFR, offers potential targets for new therapies against this difficult-to-treat disease.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Chordomas are rare bone cancers originating from notochordal remnants.
- Histologic subtypes include conventional, chondroid, and dedifferentiated chordomas.
- Current treatments face challenges due to resistance to chemotherapy and radiotherapy.
Purpose of the Study:
- To analyze the genomic landscape of chordoma.
- To identify potential pathogenic and druggable targets for novel therapies.
- To understand the genetic alterations across different chordoma subtypes.
Main Methods:
- Comprehensive molecular profiling using next-generation sequencing on 86 chordoma tumor samples.
- Identification and categorization of frequently mutated genes by histologic subtype.
- Assessment of microsatellite instability and programmed death ligand-1 (PD-L1) expression.
Main Results:
- Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) was the most common mutation (33%), followed by low-density lipoprotein receptor-related protein 1B (12%) and epidermal growth factor receptor (EGFR) (9%).
- CDKN2A/B mutations were prevalent in conventional (34%) and chondroid (33%) chordomas.
- Dedifferentiated chordomas showed high rates of CDKN2A/B and EGFR mutations (29%).
- Microsatellite instability was infrequent, and PD-L1 expression was scarce.
Conclusions:
- This study provides a detailed genomic overview of 86 chordoma samples.
- Identified frequent mutations in CDKN2A/B and EGFR present potential therapeutic targets.
- Further in vitro studies are needed to validate the functional impact of these alterations.
