RET/ptc and TRK Oncogenes in Papillary Thyroid Carcinoma

From the evidence that the oncogenes of tumor viruses could be routinely detected by their ability to induce neoplastic transformation of cells in culture, there arose the possibility that tumor cells might also contain transforming genes detectable in the same way. Gene transfer techniques (transfection) were therefore used to test the DNA of tumor cells for the presence of genes that, when introduces into cells in culture, can elicit a transformed phenotype and the ability to form tumors in animals (tumorigenicity). The first successful application of this concept was obtained with mouse fibroblasts transformed by a chemical carcinogen (Shih et al., 1979), but was then applied to a number of tumor cell lines and tumor specimens (Weinberg, 1982; Varmus, 1984; Barbacid, 1987). A transforming activity can be detected in approximately 20% of all specimens tested with some types of tumors rarely, or ever, containing transfection detectable transforming genes and others displaying consistent frequencies of activation of one or more oncogenes. The great majority of the transforming genes detected by transfection with the DNA of human cancers belongs to the family of the RAS proto-oncogenes (Barbacid, 1987).