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Updated: Jan 5, 2026
Isolation and Characterization of Tumor-initiating Cells from Sarcoma Patient-derived Xenografts
Published on: June 13, 2019
Integrated molecular characterization of chondrosarcoma reveals critical determinants of disease progression
Rémy Nicolle1, Mira Ayadi2, Anne Gomez-Brouchet3
1Programme Cartes d'Identité des Tumeurs (CIT), Ligue Nationale Contre le Cancer, Paris, France. remy.nicolle@ligue-cancer.net.
Abstract:
Chondrosarcomas are primary cancers of cartilaginous tissue with highly contrasting prognoses. These tumors are defined by recurrent mutations in the IDH genes and other genetic alterations including inactivation of CDKN2A and COL2A1; however, these have no clinical value. Here we use multi-omics molecular profiles from a series of cartilage tumors and find an mRNA classification that identifies two subtypes of chondrosarcomas defined by a balance in tumor differentiation and cell cycle activation. The microRNA classification reveals the importance of the loss of expression of the 14q32 locus in defining the level of malignancy. Finally, DNA methylation is associated with IDH mutations. We can use the multi-omics classifications to predict outcome. We propose an mRNA-only classifier to reproduce the integrated multi-omics classification, and its application to relapsed tumor samples shows the progressive nature of the classification. Thus, it may be possible to use mRNA-based signatures to detect patients with high-risk chondrosarcomas.
Insights
This study identifies distinct chondrosarcoma subtypes using multi-omics data, revealing an mRNA classifier to predict patient outcomes and detect high-risk cases.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chondrosarcomas are primary cartilaginous tissue cancers with variable prognoses.
- Known genetic alterations like IDH mutations lack clinical predictive value.
Purpose of the Study:
- To develop a multi-omics classification for chondrosarcomas.
- To identify molecular subtypes and predict patient outcomes.
- To establish an mRNA-based classifier for clinical application.
Main Methods:
- Analysis of multi-omics molecular profiles from cartilage tumors.
- Development of mRNA, microRNA, and DNA methylation classifications.
- Validation of an mRNA-only classifier on relapsed tumor samples.
Main Results:
- An mRNA classification identified two chondrosarcoma subtypes based on differentiation and cell cycle.
- MicroRNA classification highlighted the significance of 14q32 locus loss in malignancy.
- DNA methylation correlated with IDH mutations.
- Multi-omics classifications accurately predicted patient outcomes.
Conclusions:
- An mRNA-only classifier can reproduce integrated multi-omics classifications.
- The classifier demonstrates the progressive nature of chondrosarcoma.
- mRNA signatures show potential for detecting high-risk chondrosarcoma patients.
