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Updated: Aug 12, 2025
08:16
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
6.8K
Subclonal somatic copy number alterations emerge and dominate in recurrent osteosarcoma
Michael D Kinnaman1, Simone Zaccaria2,3, Alvin Makohon-Moore4,5,6,7,8
1Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Biorxiv : the Preprint Server for Biology
|January 30, 2023
Summary
Genomic profiling of osteosarcoma reveals significant intratumor heterogeneity. Specific genetic alterations, like MYC amplification, emerge in resistant clones, driving treatment failure in relapsed patients.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Osteosarcoma treatment resistance is poorly understood, particularly regarding intratumor heterogeneity.
- Spatial and temporal heterogeneity significantly impacts therapeutic outcomes in relapsed or refractory osteosarcoma.
Approach:
- Whole-genome sequencing was performed on 37 tumor samples from eight patients with relapsed/refractory osteosarcoma.
- Samples were collected from primary and metastatic/relapse sites to analyze genetic evolution.
Key Points:
- Subclonal copy number alterations were identified in most patients, indicating significant intratumor heterogeneity.
- A dominant subclone from the primary tumor often emerged in subsequent relapses.
- MYC gain/amplification was frequently observed in treatment-resistant clones (6/7 patients).
- Other potential driver genes (CCNE1, RAD21, VEGFA, IGF1R) were amplified in resistant clones.
Conclusions:
- Intratumor heterogeneity plays a crucial role in osteosarcoma progression and treatment resistance.
- Understanding these genetic dynamics can inform future therapeutic strategies for osteosarcoma.
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