Integrated molecular characterization of chondrosarcoma reveals critical determinants of disease progression

Rémy Nicolle (), Mira Ayadi, Anne Gomez-Brouchet, Lucile Armenoult, Guillaume Banneau, Nabila Elarouci, Matthias Tallegas, Anne-Valérie Decouvelaere, Sébastien Aubert, Françoise Rédini, Béatrice Marie, Corinne Labit-Bouvier, Nicolas Reina, Marie Karanian, Louis-Romée Nail, Philippe Anract, François Gouin, Frédérique Larousserie, Aurélien Reyniès and Gonzague Pinieux ()
Additional contact information
Rémy Nicolle: Ligue Nationale Contre le Cancer
Mira Ayadi: Ligue Nationale Contre le Cancer
Anne Gomez-Brouchet: Université de Toulouse
Lucile Armenoult: Ligue Nationale Contre le Cancer
Guillaume Banneau: Ligue Nationale Contre le Cancer
Nabila Elarouci: Ligue Nationale Contre le Cancer
Matthias Tallegas: Plateforme de Génétique Moléculaire des Cancers, CHRU de Tours
Anne-Valérie Decouvelaere: Centre Léon Bérard
Sébastien Aubert: CHU de Lille, Université de Lille
Françoise Rédini: Faculté de médecine
Béatrice Marie: CHU de Nancy
Corinne Labit-Bouvier: Aix Marseille Université, INSERM, MMG
Nicolas Reina: Hôpital Pierre-Paul Riquet, CHU de Toulouse
Marie Karanian: Centre Léon Bérard
Louis-Romée Nail: Faculté de médecine
Philippe Anract: Université Paris Descartes, Sorbonne Paris Cité
François Gouin: Centre Léon Bérard
Frédérique Larousserie: AP-HP, Université Paris Descartes
Aurélien Reyniès: Ligue Nationale Contre le Cancer
Gonzague Pinieux: Faculté de médecine

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12525-7

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