Molecular basis of epithelial thyroid tumorigenesis

The results of experiments carried out in different laboratories (including ours) during the last 10 years have enabled us to propose the hypothesis t hat there are different initiators able to start the epithelial thyroid tum origenic process via different pathways: - gsp and TSHR genes: at the origi n of hyperfunctioning tumours (toxic nodules and adenomas); - ras and proba bly gsp genes (in a minority of samples): via a vesicular adenoma progressi ng eventually to a vesicular carcinoma. This could be also the case for ret but only in radiation-associated tumours; - ras, ret, trk and probably gsp and met: starting from small papillary lesions ('spontaneous' or radiation -induced) and progressing to a clinically evident papillary carcinoma; - th e p53 gene playing a role only in the final dedifferentiation process. Simu ltaneous alteration in the same sample of combinations of ras, gsp, ret, tr k and TSHR was found in only a minority of the approximately 150 tumours st udied. These data suggest an interchangeable role for these genes in the in itiation of 'spontaneous' or radiation-associated epithelial thyroid tumori genesis. The requirement of one of the genes cited above to interact with o ther genes must not be neglected. Ras is the most frequently altered gene i n 'spontaneous' thyroid tumours and ret in radiation-associated thyroid tum ours. (C) 2000 Academie des sciences/Editions scientifiques et medicales El sevier SAS.