Molecular pathobiology of thyroid neoplasms.
Tumors of thyroid follicular cells provide a very interesting model to understand the development of human cancer. It is becoming apparent that distinct molecular events are associated with specific stages in a multistep tumorigenic process with good genotype/ phenotype correlation. For instance, mutations of the gsp and thyroid-stimulating hormone receptor genes are associated with benign hyperfunctioning thyroid nodules and adenomas while alterations of other specific genes, such as oncogenic tyrosine kinase alterations (RET/PTC, TRK) in papillary carcinoma and the newly discovered PAX8/peroxisome proliferator-activated receptor gamma rearrangement, are distinctive features of cancer. Although activating RAS mutations occur at all stages of thyroid tumorigenesis, evidence is accumulating that they may also play an important role in tumor progression, a role that is well documented for p53. Environmental factors (iodine deficiency, ionizing radiations) have been shown to play a crucial role in promoting the development of thyroid cancer, influencing both its genotypic and phenotypic features. It is possible that the follicular thyroid cell has unique ways to respond to DNA damage. Similarly to leukemia or sarcomas (and unlike most epithelial cancers), numerous specific rearrangements are being discovered in thyroid cancer suggesting preferential activation of DNA repair instead of cell death programs after environmentally induced genetic alterations.
Tallini
Giovanni
G
Department of Pathology Yale University School of Medicine, New Haven, CT 06510, USA. tallini@yale.edu
D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair; D016147:Genes, Tumor Suppressor; D006801:Humans; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D011989:Receptors, Thyrotropin; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases