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 thyroid carcinoma cell lines, which show a highly malignant phenotype, to cell lines deriving from differentiated thyroid carcinoma, which show a non-tumorigenic or a poorly tumorigenic phenotype. All of the parental cell lines showed impaired p53 gene function. RESULTS The cell hybrids contained alleles from the parental cell lines. All of the cell hybrids showed a lower growth rate compared with the parental undifferentiated carcinoma cell lines and were unable to grow in soft agar and to induce tumours after injection into athymic mice. CONCLUSION Taken together, these findings suggest that the highly malignant phenotype of the anaplastic thyroid carcinoma is achieved by the impairment of gene functions that negatively regulate cell growth, rather than by the activation of dominant oncogenes.