Integrated molecular characterization of chondrosarcoma reveals critical determinants of disease progression
| Autor: | Anne Gomez-Brouchet, Nicolas Reina, Matthias Tallegas, Françoise Rédini, Marie Karanian, Aurélien de Reyniès, Mira Ayadi, Corinne Labit-Bouvier, Frédérique Larousserie, Philippe Anract, Béatrice Marie, Lucile Armenoult, Guillaume Banneau, Louis-Romée Le Nail, Anne-Valérie Decouvelaere, Gonzague de Pinieux, Sébastien Aubert, Nabila Elarouci, François Gouin, Rémy Nicolle |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
DNA Copy Number Variations Science Chondrosarcoma General Physics and Astronomy Bone Neoplasms Biology Malignancy Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Recurrence CDKN2A microRNA Cancer genomics Bone cancer medicine Humans Point Mutation lcsh:Science Cell Proliferation Retrospective Studies Multidisciplinary Gene Expression Profiling Point mutation Cell Cycle food and beverages Cell Differentiation Sarcoma General Chemistry DNA Methylation Cell cycle medicine.disease Survival Analysis Gene expression profiling MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis DNA methylation Disease Progression Cancer research lcsh:Q |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-11 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Chondrosarcomas are heterogenous tumours of the bone cartilage and have highly variable prognoses. Here, the authors perform a multi-omics analysis, revealing molecular features that can stratify clinical outcomes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|