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 that there are different initiators able to start the epithelial thyroid tumorigenic process via different pathways:--gsp and TSHR genes: at the origin of hyperfunctioning tumors (toxic nodules and adenomas);--ras and probably gsp genes (in a minority of samples): via a vesicular adenoma progressing 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;--the p53 gene playing a role only in the final dedifferentiation process. Simultaneous alteration in the same sample of combinations of ras, gsp, ret, trk and TSHR was found in only a minority of the approximately 150 tumours studied. These data suggest an interchangeable role for these genes in the initiation of 'spontaneous' or radiation-associated epithelial thyroid tumorigenesis. The requirement of one of the genes cited above to interact with other genes must not be neglected. Ras is the most frequently altered gene in 'spontaneous' thyroid tumours and ret in radiation-associated thyroid tumours.
Laboratoire de génétique moléculaire UPR 42 CNRS, Institut de recherches sur le cancer-IFR Y 1221, Villejuif, France. hsuarez@infobiogen.fr
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D000242:Cyclic AMP / Q000502:physiology; D029721:Drosophila Proteins; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020917:Receptor, trkA / Q000235:genetics; D013964:Thyroid Neoplasms / Q000235:genetics*
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D000242:Cyclic AMP; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; C416649:Ret protein, Drosophila