It has also been reported that NOTCH1 is a TP53 target gene41 and as most of the immortal PPOL and HNSCC lines have TP53 mutations this could be an additional mechanism of its inactivation and is consistent with the altered regulation of hairy enhancer of split 2 (HES2) in these lines12,41. The gene discussed is TP53; the disease is head and neck squamous cell carcinoma.