Transcriptome analysis reveals molecularly distinct subtypes in retinoblastoma

Retinoblastoma is the most frequent intraocular malignancy in children. Little is known on the molecular basis underlying the biological and clinical behavior of this cancer. Here, using gene expression profiles, we demonstrate the existence of two major retinoblastoma subtypes that can be divided into six subgroups. Subtype 1 has higher expression of cone related genes and higher percentage of RB1 germline mutation. By contrast, subtype 2 tumors harbor more genes with ganglion/neuronal features. The dedifferentiation in subtype 2 is associated with stemness features including low immune infiltration. Gene Otology analysis demonstrates that immune response regulations and visual related pathways are the key molecular difference between subtypes. Subtype 1b has the highest risk of invasiveness across all subtypes. The recognition of these molecular subtypes shed a light on the important biological and clinical perspectives for retinoblastomas.