ONCOGENES AND ANTIONCOGENES INVOLVED IN HUMAN THYROID CARCINOGENESIS

The development of cancer is due to the accumulation of multiple somat ic mutations, in some cases following germline mutations, which occur in hereditary malignancies such as retinoblastomas or multiple endocri ne neoplasia (MEN 2A and B), Genetic alterations or changes in the exp ression of growth regulatory genes can lead to the initiation of malig nant transformation and to eventual tumor progression, Cells that have undergone these cumulative alterations in either the structure or exp ression of these regulatory genes generally possess a selective growth and/or metastatic advantage over other normal non-transformed cells. Thus, activation of dominantly transforming oncogenes by point mutatio ns, gene amplification, chromosomal translocation or insertional mutag enesis can lead to uncontrolled cellular growth or to a disruption in normal differentiation or apoptosis. Equally contributory to the proce ss of malignant progression is the inactivation of recessive tumor sup pressor genes due to point mutations and/or loss of heterozygosity in one allele, which can ultimately lead to a reduction of homozygosity i n both alleles, Thyroid tumors in humans represent a particularly suit able multistage model of epithelial tumorigenesis. In fact, even thoug h most thyroid neoplasms originate from a single cell type, i.e. the t hyroid follicular cell, they include a broad spectrum of tumors with d ifferent phenotypic characteristics and variable biological and clinic al behaviour. Multiple degrees of malignancies have been defined: from the benign colloid adenomas through the slowly progressive differenti ated papillary and follicular carcinomas to the invariably fatal anapl astic carcinomas, although these histological changes are not necessar ily sequential. In this review an effort has been made to summarize an d integrate new data published on genetic lesions and altered expressi on of genes involved in the tumorigenesis of the follicular type of th yroid cancer, We have focused our interest only on gene alterations in ducing gain or loss of function, that have been studied in vivo in hum an thyroid tumor specimens by the use of different techniques, such as PCR mediated DNA analyses, sequencing, mRNA level evaluation and prot ein expression by immunohistochemical staining.