%0 Journal Article %T A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression %+ Biologie Cellulaire et Cancer %+ (le programme) Cartes d'identité des tumeurs (CIT) %+ Hospital Nacional de Pediatría J.P. Garrahan %+ Synergie Lyon Cancer-Platform of Bioinformatics-Gilles Thomas %+ Centre Léon Bérard [Lyon] %+ Département de Biologie des Tumeurs %+ Institut Curie [Paris] %+ Institut de la Vision %+ Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe %+ Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB %+ Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI) %+ Signalisation, radiobiologie et cancer %+ Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ) %+ Hôpital Bretonneau %+ Unité de génétique et biologie des cancers (U830) %+ Département de Recherche Translationnelle %+ Centre de recherche de l'Institut Curie [Paris] %+ Genomics Consulting (GeCo) %+ Institut de Recerca Pediàtrica Hospital Sant Joan de Déu [Barcelona, Spain] %+ Hospital Sant Joan de Déu [Barcelona] %+ Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET) %+ CHU Rouen %+ Département d'Imagerie Médicale [Institut Curie] %+ Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST) %+ Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)) %+ CHI Créteil %A Liu, Jing %A Ottaviani, Daniela %A Sefta, Meriem %A Desbrousses, Céline %A Chapeaublanc, Elodie %A Aschero, Rosario %A Sirab, Nanor %A Lubieniecki, Fabiana %A Lamas, Gabriela %A Tonon, Laurie %A Dehainault, Catherine %A Hua, Clément %A Fréneaux, Paul %A Reichman, Sacha %A Karboul, Narjesse %A Biton, Anne %A Mirabal-Ortega, Liliana %A Larcher, Magalie %A Brulard, Céline %A Arrufat, Sandrine %A Nicolas, André %A Elarouci, Nabila %A Popova, Tatiana %A Némati, Fariba %A Decaudin, Didier %A Gentien, David %A Baulande, Sylvain %A Mariani, Odette %A Dufour, Florent %A Guibert, Sylvain %A Vallot, Céline %A Rouic, Livia Lumbroso-Le %A Matet, Alexandre %A Desjardins, Laurence %A Pascual-Pasto, Guillem %A Suñol, Mariona %A Catala-Mora, Jaume %A Llano, Genoveva Correa %A Couturier, Jérôme %A Barillot, Emmanuel %A Schaiquevich, Paula %A Gauthier-Villars, Marion %A Stoppa-Lyonnet, Dominique %A Golmard, Lisa %A Houdayer, Claude %A Brisse, Hervé %A Bernard-Pierrot, Isabelle %A Letouzé, Eric %A Viari, Alain %A Saule, Simon %A Sastre-Garau, Xavier %A Doz, François %A Carcaboso, Angel %A Cassoux, Nathalie %A Pouponnot, Celio %A Goureau, Olivier %A Chantada, Guillermo %A de Reyniès, Aurélien %A Aerts, Isabelle %A Radvanyi, François %< avec comité de lecture %@ 2041-1723 %J Nature Communications %I Nature Publishing Group %V 12 %N 1 %P 1-20 %8 2021-12 %D 2021 %R 10.1038/s41467-021-25792-0 %M 34552068 %Z Life Sciences [q-bio]/CancerJournal articles %X Retinoblastoma is the most frequent intraocular malignancy in children, originating from a maturing cone precursor in the developing retina. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using multi-omics data, we demonstrate the existence of two retinoblastoma subtypes. Subtype 1, of earlier onset, includes most of the heritable forms. It harbors few genetic alterations other than the initiating RB1 inactivation and corresponds to differentiated tumors expressing mature cone markers. By contrast, subtype 2 tumors harbor frequent recurrent genetic alterations including MYCN -amplification. They express markers of less differentiated cone together with neuronal/ganglion cell markers with marked inter- and intra-tumor heterogeneity. The cone dedifferentiation in subtype 2 is associated with stemness features including low immune and interferon response, E2F and MYC/MYCN activation and a higher propensity for metastasis. The recognition of these two subtypes, one maintaining a cone-differentiated state, and the other, more aggressive, associated with cone dedifferentiation and expression of neuronal markers, opens up important biological and clinical perspectives for retinoblastomas. %G English %2 https://hal.science/hal-03374490/document %2 https://hal.science/hal-03374490/file/2021_Jing_Liu.pdf %L hal-03374490 %U https://hal.science/hal-03374490 %~ INSERM %~ PASTEUR %~ ENSMP %~ EPHE %~ UNIV-TOURS %~ CNRS %~ UNIV-LYON1 %~ ENSMP_CBIO %~ PARISTECH %~ U968 %~ FNCLCC %~ CURIE %~ CORDELIERS %~ UMR144 %~ COMUE-NORMANDIE %~ PSL %~ UNIV-PARIS-SACLAY %~ ENSMP_DEP_MS %~ CRCL %~ SORBONNE-UNIVERSITE %~ SORBONNE-UNIV %~ SU-MEDECINE %~ SU-SCIENCES %~ TEST-DEV %~ UDL %~ UNIV-LYON %~ UNIV-PARIS %~ UNIVERSITE-PARIS %~ UP-SANTE %~ TEST-HALCNRS %~ ENSMP-PSL %~ EPHE-PSL %~ INSTITUT-CURIE-PSL %~ UNIVERSITE-PARIS-SACLAY %~ SU-TI %~ GS-LIFE-SCIENCES-HEALTH %~ GS-HEALTH-DRUG-SCIENCES %~ ALLIANCE-SU %~ INRIAARTDOI %~ TEST3-HALCNRS