A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2021

A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression

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Céline Desbrousses
Elodie Chapeaublanc
Nanor Sirab
Clément Hua
Sacha Reichman
Odette Mariani
Florent Dufour
Céline Vallot
Isabelle Bernard-Pierrot
Celio Pouponnot
François Radvanyi

Abstract

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.
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hal-03374490 , version 1 (21-11-2022)

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Jing Liu, Daniela Ottaviani, Meriem Sefta, Céline Desbrousses, Elodie Chapeaublanc, et al.. A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression. Nature Communications, 2021, 12 (1), pp.1-20. ⟨10.1038/s41467-021-25792-0⟩. ⟨hal-03374490⟩
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