The role of hedgehog signalling in tumorigenesis

Well differentiated thyroid carcinomas provide a unique model of human, epithelial cell carcinogenesis. Their molecular characterization has allowed to associate specific genetic alterations to the two papillary and follicular histotypes which, despite their common origin, display different biological and clinical behaviors. A common mechanism of oncogenic activation has been observed in these tumors, based on the peculiar characteristic of thyroid epithelium to generate fusion transforming genes by chromosomal rearrangements. The reasons for this peculiar uniqueness of thyrocytes are not known, but a structural explanation, based on the spatial contiguity in the interphase nuclei of thyrocytes of the two fused genes and enzymatic features of these cells which render them apoptosis resistant to DNA damage, have been proposed to account for this behavior.