Cytogenetic and Molecular Events in Adenoma and Well-differentiated Thyroid Follicular-cell Neoplasia

In spite of its simple organization, the thyroid gland can give rise to a wide spectrum of neoplasms, ranging from innocuous to highly malignant lesions. Approximately 94% of the malignancies is represented by well-differentiated thyroid carcinoma originating from follicular cells. These neoplasms are divided into two main categories, papillary thyroid carcinoma and follicular thyroid carcinoma. Despite their origin from the same type of cells, the two neoplasias show different biological behavior and a different set of genetic features, including specific cytogenetic patterns. Thyroid adenoma is the benign counterpart of follicular carcinoma. No benign counterpart of papillary carcinoma has yet been identified. The chromosomes of thyroid nodules have been investigated since 1965, and different cytogenetic subgroups have been recognized, some of which show structural chromosomal rearrangements. These structural changes lead to the formation of fusion genes RET-PTC, TRK(-T), and BRAF-AKAP9, which originate as a result of intrachromosomal or interchromosomal rearrangements and are found in papillary thyroid carcinoma. Fusion genes involving PPARγ are caused mainly by translocations and are characteristic of follicular neoplastic tissue. Radiation exposure and the particular architectural arrangement of chromatin regions in which the affected genes lie during interphase are thought to favor the formation of fusion genes in papillary thyroid carcinoma and possibly also in follicular thyroid carcinoma.