The highly malignant phenotype of anaplastic thyroid carcinoma cell lines is recessive

Objective: The aim of our studies was to determine whether the phenotype of the anaplastic thyroid carcinomas is dominant or recessive. In fact, it is hypothesized, on the basis of epidemiological and pathological data, that undifferentiated thyroid carcinomas are derived from differentiated tumours through a mechanism of tumour progression. Design: Cell hybrids have been generated by cell fusion of anaplastic thyro id carcinoma cell lines, which show a highly malignant phenotype, to cell l ines deriving from differentiated thyroid carcinoma, which show a non-tumor igenic or a poorly tumorigenic phenotype. All of the parental cell lines sh owed impaired p53 gene function. Results: The cell hybrids contained alleles from the parental cell lines. A ll of the cell hybrids showed a lower growth rate compared with the parenta l undifferentiated carcinoma cell lines and were unable to grow in soft aga r and to induce rumours after injection into athymic mice. Conclusion: Taken together, these findings suggest that the highly malignan t phenotype of the anaplastic thyroid carcinoma is achieved by the impairme nt of gene functions that negatively regulate cell growth, rather than by t he activation of dominant oncogenes.