Ras oncogene mutations in benign and malignant thyroid neoplasms.

Current models for tumorigenesis propose that a series of genetic alterations occur during the progression from the normal cell to the malignant phenotype. Mutations in each of the three ras genes (K-ras, H-ras, and N-ras) have been identified in many human neoplasms, including thyroid cancer. In this study we examined genomic DNA from benign and malignant thyroid neoplasms for mutations that are known to activate the ras oncogenes (codons 12, 13, and 61). DNA from frozen surgically excised tissue (n = 8) and from formalin-fixed paraffin-embedded tissue (n = 30) was amplified by the polymerase chain reaction and screened for mutations using oligonucleotide-specific hybridization. No mutations were identified in follicular adenomas (n = 9). In follicular carcinomas, 2 of 14 tumors contained mutations (N-ras 61, Gln to Arg), and both of these patients had bone metastases. One of 15 papillary carcinomas had a ras mutation (H-ras 12, Gly to Ser). In contrast to other studies, we found that ras mutations are relatively uncommon in both benign and malignant thyroid neoplasms. Studies of larger numbers of tumors and comparisons of different patient populations will be required to assess a possible association of mutations in N-ras 61 with clinically aggressive follicular cancer.

[1]  S. Rubin,et al.  Point mutations of ras oncogenes are an early event in thyroid tumorigenesis. , 1990, Molecular endocrinology.

[2]  J. Fagin,et al.  Clonal composition of benign and malignant human thyroid tumors. , 1990, The Journal of clinical investigation.

[3]  J. Fagin,et al.  H-ras protooncogene mutations in human thyroid neoplasms. , 1990, The Journal of clinical endocrinology and metabolism.

[4]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[5]  B. Caillou,et al.  Presence of mutations in all three ras genes in human thyroid tumors. , 1990, Oncogene.

[6]  M. Santoro,et al.  PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas , 1990, Cell.

[7]  N. Lemoine,et al.  Papillary and follicular thyroid carcinomas show a different pattern of ras oncogene mutation. , 1989, British Journal of Cancer.

[8]  J. L. Bos,et al.  ras oncogenes in human cancer: a review. , 1989, Cancer research.

[9]  J. Willey,et al.  Differential DNA sequence deletions from chromosomes 3, 11, 13, and 17 in squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma of the human lung. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[10]  N. Lemoine,et al.  High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. , 1989, Oncogene.

[11]  G. Thomas,et al.  The clonal origin of thyroid nodules and adenomas. , 1989, The American journal of pathology.

[12]  F. Wyllie,et al.  Activated ras oncogenes in human thyroid cancers. , 1988, Cancer research.

[13]  G. Mufti,et al.  Mutation of Ki-ras and N-ras oncogenes in myelodysplastic syndromes. , 1988, Blood.

[14]  M. Santoro,et al.  A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases , 1987, Nature.

[15]  J. Bos,et al.  A dot-blot screening procedure for mutated ras oncogenes using synthetic oligodeoxynucleotides. , 1986, Gene.

[16]  B. Vogelstein,et al.  Purification of DNA from formaldehyde fixed and paraffin embedded human tissue. , 1985, Biochemical and biophysical research communications.

[17]  E. Chen,et al.  Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue , 1983, Nature.