Two subtypes of retinoblastoma identified

Researchers from the Institut de Recerca Sant Joan de Déu have collaborated in a study, published in Nature Communications, which has identified two subtypes of molecular retinoblastoma with different genomic, clinical and pathological features.

The human eye is mainly made up of the pupil, the cornea, the iris, and the retina (among others). The retina is the innermost layer of the eyeball and its function is to transform the light it receives into a nerve impulse, so the brain transforms it into the images we see.

Certain genetic mutations in retinal cells can lead to the development of retinoblastoma, the most frequent intraocular malignancy in children, with an incidence rate of about one in 17,000 live births.

¿How is the retinoblastoma originated?

The retina is made up of 6 types of neurons (nervous tissue). The cone is one of these types, and many studies have shown that retinoblastoma originates from a maturing cone precursor in the developing retina. And, generally, the mutation is an inactivation of the suppressor gene called RB1.

However, three studies based on gene expression profiling reached conflicting conclusions concerning the possible existence of retinoblastoma molecular subtypes and the retinal cell type-specific markers of retinal cells expressed in retinoblastoma. Therefore, today, there is a lack of a molecular framework for understanding the biology and clinical behavior of this cancer.

The two subtypes of retinoblastoma

Researchers have analyzed more than 100 retinoblastomas and have identified two subtypes with different genomic, clinical and pathological features such as the age of diagnosis, heredity or the way the tumor grows.

Retinoblastoma 1 subtypes have fewer genetic alterations in the cells of the retina than subtype 2. In contrast, retinoblastoma 2 subtypes are more aggressive, have a higher risk of metastasis, and are more resistant to certain therapies. The difference between the two subtypes also lies in the state of cone differentiation and expression of neuronal / ganglion cell markers.

"This study opens up new biological and clinical perspectives for retinoblastomas since it will help improve its diagnosis, prognosis, choose more specific treatments and design new ones," says Dr. Jaume Català Mora, researcher at the Pediatric ophthalmology group at the Institut de Recerca Sant Joan de Déu and pediatric ophthalmologist at the SJD Barcelona Children's Hospital.

The SJD Barcelona Children's Hospital, world reference in the innovative treatment of retinoblastoma

Currently, the main therapeutic objective for retinoblastoma is first to save the child's life through early detection, treatment of the ocular tumor and prevention of metastatic spread. Secondary goals are eye preservation and maximization of visual potential.

In this context, a team of researchers from Sant Joan de Déu and the biotechnology company VCN Biosciences has developed a world first treatment with an oncolytic virus. The treatment is a modified adenovirus that identifies, infects and multiplies inside cancer cells. The oncolytic virus VCN-01 selectively attacks cancer cells while leaving healthy cells unharmed.

The study that has identified the two subtypes of retinoblastoma has been led by the Curie Institute (CNRS) with the collaboration of the University of Paris, the Hospital J.P Garrhan of Buenos Aires, the "Gilles Thomas" Bioinformatics Platform and the SJD Barcelona Childre'n's Hospital · Institut de Recerca Sant Joan de Déu, with the participation of the researchers Mariona Suñol, Genoveva Correa Llano, Angel Montero Carcaboso, Guillem Pascual-Pasto, Guillermo Chantada and Jaume Català-Mora.

Reference paper

Liu, J., Ottaviani, D., Sefta, M. et al. A high-risk retinoblastoma subtype with stemness features, dedifferentiated cone states and neuronal/ganglion cell gene expression. Nat Commun 12, 5578 (2021). https://doi.org/10.1038/s41467-021-25792-0.