To examine how EZH2 function is affected by neoplastic transformation, we characterised three cellular states generated by sequential modification of primary fibroblasts: untransformed cells, immortalised by expression of human telomerase (hTERT) to avoid confounding effects associated with replicative senescence of primary cell populations; pre‐neoplastic cells, with inactivated p53 and pRb, but lacking tumorigenic potential; and transformed cells, which also express oncogenic HRASv12 and induce tumour formation when injected into immunocompromised mice (Fig 1A) 34. This evidence concerns the gene RB1 and neoplasm.