Technical Report No. 3-92
Unique association of p53 mutations with undifferentiated but not with differentiated thyroid gland carcinomas
Ito T, Seyama T, Mizuno T, Tsuyama N, Hayashi T, Hayashi Y, Dohi K, Nakamura N, Akiyama MEditor’s note: Publications based on this report were published in Cancer Res 52:1369-71, 1992, and Jpn J Cancer Res 84:526-31, 1993.
Summary
Thyroid neoplasms show a wide variety of lesions varying from slowly growing differentiated adenocarcinomas to rapidly proliferating undifferentiated carcinomas. There is some histopathological evidence that the undifferentiated thyroid carcinomas are derived from differentiated carcinomas. Moreover, it is suspected that some genetic events might be associated with such changes. In the present study, mutations in the p53 gene were detected by direct sequencing analysis after polymerase chain reaction amplification of exons 5-8, using paraffin-embedded primary tumors and cultured cells.
No mutations in exons 5 to 8 were detected in 10 differentiated papillary adenocarcinomas, whereas 6 out of 7 undifferentiated carcinomas were found to carry base substitution mutations. Sequencing analysis confirmed mutations at codons 135 (from TGC to TGT), 141 (from CCC to CCT), 178 (from CAC to GAC), 213 (from CGA to TGA), 248 (from CGG to CAG, from CGG to TGG), and 273 (from CGT to TGT). The spectrum of mutations (G:C to A:T transitions in 7 of 8) might be a specific feature of the spontaneous cancers. The results strongly suggest that, in human thyroid glands, p53 mutations play a crucial role in the progression of differentiated carcinomas to undifferentiated ones.
Thyroid neoplasms show a wide variety of lesions varying from slowly growing differentiated adenocarcinomas to rapidly proliferating undifferentiated carcinomas. There is some histopathological evidence that the undifferentiated thyroid carcinomas are derived from differentiated carcinomas. Moreover, it is suspected that some genetic events might be associated with such changes. In the present study, mutations in the p53 gene were detected by direct sequencing analysis after polymerase chain reaction amplification of exons 5-8, using paraffin-embedded primary tumors and cultured cells.
No mutations in exons 5 to 8 were detected in 10 differentiated papillary adenocarcinomas, whereas 6 out of 7 undifferentiated carcinomas were found to carry base substitution mutations. Sequencing analysis confirmed mutations at codons 135 (from TGC to TGT), 141 (from CCC to CCT), 178 (from CAC to GAC), 213 (from CGA to TGA), 248 (from CGG to CAG, from CGG to TGG), and 273 (from CGT to TGT). The spectrum of mutations (G:C to A:T transitions in 7 of 8) might be a specific feature of the spontaneous cancers. The results strongly suggest that, in human thyroid glands, p53 mutations play a crucial role in the progression of differentiated carcinomas to undifferentiated ones.