MOLECULAR-GENETICS OF THYROID-CANCER

Tumors of the human thyroid follicular cell demonstrate multiple ''routes'' and multiple stages of development, offering an unparalleled opportunity for correlating clinicopathologic tumor behavior with the underlying molecular genetic abnormalities. This review summarizes the clinical and experimental evidence supporting the causal role of five key genes in thyroid oncogenesis, namely, the oncogenes ras, gsp, ret, and trk and the tumor-suppressor gene TP53. The nature of the somatic mutations is described and the likely mechanisms discussed by which they perturb cellular growth signal transduction to produce particular pathologic phenotypes. A model of thyroid oncogenesis is presented that suggests that the pattern of tumor development is determined by the nature of the initiating oncogenic event.