Point mutations of ras and Gs alpha subunit genes in thyroid tumors.

We studied 43 thyroid tumors including 5 adenomatous goiters, 7 follicular adenomas, 22 papillary carcinomas, and 9 medullary carcinomas with regard to the presence of point mutations in the genes of Gs alpha subunit (Gs alpha), Gi2 alpha subunit (Gi2 alpha), H-ras, K-ras, and N-ras by a polymerase chain reaction-direct sequencing method. An adenomatous goiter and a follicular adenoma showed double mutations at codon 227 and 231, and 4 papillary carcinomas showed mutation at codon 231 of the Gs alpha gene. An adenomatous goiter, a follicular adenoma, and a papillary carcinoma showed a missense mutation in codon 13 of the K-ras gene. There were no such missense mutations of these G-protein or ras genes in medullary carcinomas. These data indicate that the genetic events involved in the oncogenesis of parafollicular C-cells are different from those of thyroid follicular cells, in which missense mutations of Gs alpha and ras genes seem to play important roles in tumorigenesis.