MYCN and retinoblastoma: In contrast to the previously described hypermethylation pattern12,16 of subtype 2 retinoblastoma, this subtype 2-MYCN (cluster C) was characterized by hypomethylation and showed distinct patterns of genomic rearrangements, gene expression profiles and clinical characteristics to cluster B, underlining biological differences between these two clusters within subtype 2 (Fig. 7).