This possibility is supported by the reports that simultaneous activation of Ras and Hh signalling caused extensive formation of intraepithelial neoplasias and accelerated lethality in a transgenic model of pancreatic carcinoma (Pasca di Magliano et al, 2006) and that de-regulation of Ras signalling in mice lacking p53 increased Shh expression (Hingorani et al, 2005). This evidence concerns the gene TP53 and intraepithelial neoplasia.