In unsupervised methylation analysis, the O-PDXs and iPSC-RBs overlapped with retinoblastomas/pineal tumors from a reference collection of 2901 brain tumor methylation profiles29 and they were clearly separated from the normal retinal organoids and iPSCs in tSNE plots (Fig. 4H–K and Supplementary Data 5). This evidence concerns the gene ESCO2 and brain neoplasm.